Screw the Woo Woo: Apple Cider Vinegar

This is an oldie that keeps cropping up in the sphere of (completely unvetted) wellness tips – apple cider vinegar. I’m a bit puzzled by the claims that this is a “natural remedy.” Apples are natural. Cider is processed, as is vinegar, through a fermentation process involving bacteria and yeast that occurs on an industrial scale. It’s not magic. It’s chemistry.

Anyway, a Google search revealed top hits chock a block FULL of Woo Woo claims that are fantastical in nature and, you guessed it, not scientifically vetted. The “apple cider vinegar process” is only at the top because I searched for it first, I suspect. But the rest – “apple cider vinegar gummies” (gross!), “apple cider vinegar benefits” (makes foods taste yummo, but that’s it), “apple cider vinegar pills” (WTF?), “apple cider vinegar weight loss” (maybe if all you eat are salads with apple cider vinaigrette dressing – but that’s a sad way to live), and “apple cider vinegar diet” (that doesn’t even make sense) – it’s all a bunch of doo doo!

“My grandfather’s work was doo doo!” Young Frankenstein. Photo source.

But, since I’m a debunker of woo woo scams, I’m doing the research. A PubMed (database of peer-reviewed published biomedical research) search using “apple cider vinegar” yielded 94 results. Aside from a few articles on the antimicrobial and anti-fungal properties of ACV (not surprising, considering that ACV contains 5-6% acetic acid) and studies in rodent models (cardiovascular health, obesity, and something about boosting immunity in carp and – those were weird) that may or may not translate to humans, most of the articles covered the dangers of using ACV as a “natural remedy.”

Photo credit here.

For example, tooth erosion and esophageal injury was documented in at least two studies [Case Reports Ned Tijdschr Tandheelkd. 2012 Dec;119(12):589-91. doi: 10.5177/ntvt.2012.12.12192 “Unhealthy weight loss. Erosion by apple cider vinegar”; J Am Diet Assoc. 2005 Jul;105(7):1141-4. doi: 10.1016/j.jada.2005.04.003. “Esophageal injury by apple cider vinegar tablets and subsequent evaluation of products.”]. Seriously, do NOT use this to treat heartburn or GERD. It’s a fucking ACID and adding ACID to a condition caused by escape of stomach ACID is completely ridiculous. Don’t drink it. Cook with it, but don’t drink it.

Not only does ACV have no benefit for atopic dermatitis [(skin irritation) Pediatr Dermatol 2019 Sep;36(5):634-639. doi: 10.1111/pde.13888. Epub 2019 Jul 22. Apple cider vinegar soaks [0.5%] as a treatment for atopic dermatitis do not improve skin barrier integrity], topical skin treatments with ACV can cause chemical burns [J Am Acad Dermatol. 2012 Oct;67(4):e143-4. doi: 10.1016/j.jaad.2011.11.934. “Chemical burn from topical apple cider vinegar.”]! Don’t put it on your skin. Please.

One study reported a lack of antiglycemic (lowering of blood sugar) by vinegar, including ACV, in humans [Nutr Res. 2009 Dec;29(12):846-9. doi: 10.1016/j.nutres.2009.10.021. “Vinegar lacks antiglycemic action on enteral carbohydrate absorption in human subjects.”]. So no, it won’t help people with diabetes.

Apple cider vinegar and a paper funnel inserted into a cup are used as an at home fruit fly trap. Photo credit here.

Fun rando fact – apparently ACV attracts several species of fruit flies, so if you want to collect some wild ones as pest control or for DIY experiments at home, try it! I’m not citing these. Look it up yourself. There are a surprising number of studies documenting this.

Bottom line – there are no validated health benefits in humans for this “natural remedy,” but there are plenty of bad things that can happen if you drink a lot of cider vinegar, put it on your skin, or take pills (and presumably gummies).

And ACV does NOT cure or treat cancer. Only two references came up in a PubMed search for “apple cider vinegar cancer,” and neither reported any benefits for treatment of warts or moles, let alone skin cancer.

BUT…ACV can make tasty salad dressings and delicious sauces. One of my favorites for fall is apple glazed baked chicken. Here’s the recipe:

Ingredients:

1 whole broiler chicken, apple jelly, apple cider vinegar, apple pie spice, apples (tart or sweet)

Recipe

Preheat oven to 325 degrees. Season the chicken with olive oil, salt, and pepper. Bake chicken for 1 1/2-2 hours. While chicken is baking, slice apples and prepare glaze. To prepare glaze, heat 1/2 jar of apple jelly with an equal volume of apple cider vinegar and 1-2 teaspoons of apple pie spice. Boil until volume is reduced by 1/2. Remove chicken from oven, drain chicken stock (can be used to prepare some DELICIOUS rice), cover with glaze, and place apple slices around chicken in the baking dish. Cook another 1/2 hour or until chicken is done. Serve with rice or potatoes, green beans, and enjoy!

Yo, Cancer Researcher – What the Heck Do You Actually Do?

Photo source here.

It occurred to me that while I’ve told you that I’m a cancer researcher, you might not know what that actually means. There are many kinds of researchers who conduct many diverse types of cancer research, as detailed here. All are important and complimentary, and they often overlap. I am an academic (work at a University) laboratory researcher in the broad field of Cell Biology, with a focus on Cancer Biology and Cancer Treatment research, specifically working as a “wet lab” researcher. This means I conduct and supervise hands-on experimental research with cells in a dish, mouse models, and tissue/cell extracts (where we grind up or pulverize tissues and cells, separate them into their components like DNA, RNA, or protein, and analyze them using molecular biology or biochemistry). Other researchers use computational models and datasets to conduct their “dry lab” research.

Analysis of EPHA2 expression in human breast cancer patients correlated with poor overall survival. Source here.

Both types of research are important, and one informs and shapes the other. For example, I’ll use information found in large databases generated by dry labs that containing data from actual human cancers (e.g. cBioPortal for Cancer Genomics, Kaplan-Meier plotter, and The Human Cancer Metastasis Database) to find clues about how the gene product molecules I study might be driving cancer cell growth, survival, and invasion. The data I generate then feeds back into these databases, linking known functions in laboratory models along with data about where these gene product molecules are expressed and at what level in human cancers. In fact, all of the cancer research fields listed in the link feed into and fuel each other. Science these days is multi-disciplinary, meaning scientists from diverse fields bring their expertises to the table in order to do better, more advanced, more impactful science. Case in point – I’m working with Dr. Craig Duvall, Biomedical Engineer right now, applying his cutting-edge nanoparticle and carrier technologies to targeting the expression of cancer-driving genes in the cell culture and mouse models in my laboratory.

What is it exactly that you do do? Young Frankenstein, one of the BEST films of all time!

So, what is it exactly that I do…do?

These days, I split my time between the bench (doing actual experiments, which is why I became a scientist in the first place) and the office (doing endless paperwork as quickly and as efficiently as possible so I can get back to the bench). I also supervise a phenomenal medical student and co-mentor insanely smart graduate students, support and collaborate with a team of amazing junior and senior faculty, write grant proposals (more on that below), write up scientific findings into manuscripts for peer review and publication, prepare and deliver scientific talks, maintain compliance (biosafety, environmental safety, radiation safety, responsible care and use of laboratory animals, etc.), make sure the laboratory staff have what they need to perform their research, make sure equipment gets serviced and is operational, attend faculty meetings, scientific seminars, professional development meetings, student thesis committee meetings.

Meme source here.

Lots of meetings…

As far as what I research, I use cell culture and mouse models of breast cancer, including metastatic breast cancer, to test new experimental therapeutics.

Experimental Drug (left) getting into tumor cells in 3D culture better than control (right). Source here.

The goal is to discover more specific, effective, less toxic (looking at you, chemo) treatments for breast cancer. I’ll blog more about specific projects later, but what this normally involves is seeing if the new drug makes cancer cells in a petri dish stop growing and/or die, stops cancer cells in a dish from moving and invading, and if a new drug stops tumors in mice from growing or kills them, and, better yet, if the new drugs can actually shrink the tumors. For more information, see the copy of my NIH Biosketch, the mini-resume that we add to every grant application to prove our published expertise, pasted below.

Lung metastases (green) in mouse. The left panel is control and the right is from a mouse lacking ephrin-A1 expression. Source here.

How did I become a cancer researchers? Lots of school and training! I earned a B.A. in Biology from Maryville College in 1995. After graduating, I completed graduate studies at Vanderbilt University, earning a Ph.D. in Cell Biology in 2000. After graduate studies, I completed postdoctoral training in the laboratory of Jin Chen at Vanderbilt University Medical Center from 2000-2003, supported by an American Heart Association Postdoctoral Fellowship Award (I was studying tumor blood vessels, so it was legit!) and a Department of Defense Breast Cancer Research Program Postdoctoral Fellowship award, before being promoted to Research Instructor. I was promoted to Research Assistant Professor in 2006, and during that time I earned a K01 career transition award from the National Institutes of Health/National Cancer Institute. (NIH/NCI – the major funding agency for biomedical cancer research in the united states). This led to my first NIH/NCI independent investigator R01 award in 2011. I was promoted to Assistant Professor of Medicine, Tenure Track, in 2015, and am still at Vanderbilt University Medical Center. I am currently supported by 2 NIH/NCI R01 grants as well as funds from my institution that allow me to generate preliminary data necessary to apply for more grants.

Have you spotted a theme? The theme is “grants” or “awards.” One of the most important jobs I have for my research laboratory is to successfully apply for grants – meaning I write up a proposal about the cool science I want to do, explaining how and why it will benefit patients with breast cancer and move the field forward, and I submit it to the funding agency and compete with a bunch of other super smart, top notch scientists for limited research dollars. These days, money is tough to come by. When I first entered the field as an independent scientist, the top 15% of NCI applications were funded (compared with a funding rate of 25% earlier). These days, it’s at 10%. My colleagues and I literally just missed out on getting a really innovative research proposal funded by 1%! I’m worried how Covid-19 will affect funding over the next 5-10 years, too, as are most of my colleagues. Why is that important? Well, if we want the U.S. to remain on the cutting edge of research and innovation, and if we want to keep discovering new and better ways to detect and treat cancer, we need to invest in science, especially academic science. If you are a cancer survivor, know a survivor, or just want to make the world a better place with less cancer, write your representatives Congress to let them know you want support and full funding of the National Institutes of Health and the National Cancer Institute.

Biographical Sketch

OMB No. 0925-0001 and 0925-0002 (Rev. 10/15 Approved Through 10/31/2018)

NAME: Dana M. Brantley-Sieders

eRA COMMONS USER NAME (credential, e.g., agency login): BRANTLDM

POSITION TITLE: Assistant Professor, Medicine/Rheumatology, Vanderbilt University School of Medicine

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)

INSTITUTION AND LOCATIONDEGREE (if applicable)  Completion Date MM/YYYY  FIELD OF STUDY  
Maryville College, Maryville, TennesseeB.A.05/1995Biology
Vanderbilt University School of MedicinePh.D.06/2000Cell Biology
Vanderbilt University Medical CenterPostdoctoral07/2000Cancer Biology

A. Personal Statement

I have the expertise, leadership, training, and motivation to successfully carry out the proposed investigation of how EphA2 receptor tyrosine kinase contributes to breast cancer bone metastasis, particularly in terms of tumor-osteoclast interactions that mediate osteolysis in clinically relevant in vivo models that mimic human breast-to-bone metastasis. I have a broad background in cancer research, with specific training and expertise in mouse models of breast cancer and host-tumor interactions (genetically engineered mouse models and orthotopic allograft/xenograft models, including PDX), as well as three-dimensional cell culture and co-culture models, and data mining human tissue microarray and patient datasets to validate clinical relevance of findings in my laboratory model systems. I also have experience testing novel experimental therapeutics in clinically relevant models of breast cancer, including metastatic disease. My research includes analysis of breast cancer cell growth (multiple molecular subtypes), survival, invasion, and host-tumor interactions. Dr. Sterling, Dr. Pellecchia, and I have established a fruitful collaboration that will continue as a part of this exciting investigation

  1. Werfel, T.A., Wang, S., Jackson, M.A., Kavanaugh, T.E., Joly, M.M., Lee, L.H., Hicks, D.J., Sanchez, V., Ericsson, P.G., Kilchrist, K.V., Dimobi, S.C., Sarett, S.M., Brantley-Sieders, D.M., Cook, R.S., and Duvall, CL. (2018) Selective mTORC2 Inhibitor Therapeutically Blocks Breast Cancer Cell Growth and Survival. Cancer Res 78:1845-1858. PMID: 29358172. PMCID: PMC5882532.
  2. Sarett, S.M., Werfel, T.A., Lee, L., Jackson, M.A., Kilchrist, K.V., Brantley-Sieders, D., and Duvall, C.L. (2017) Lipophilic siRNA targets albumin in situ and promotes bioavailability, tumor penetration, and carrier-free gene silencing. PNAS 114: E6490-E6497. doi: 10.1073/pnas.1621240114. Epub 2017 Jul 24. PMID: 28739942. PMCID: PMC5558996.
  3. Song, W., Hwang, Y., Youngblood, V.M., Cook, R.S., Balko, J.M., Chen, J., and Brantley-Sieders, D.M. (2017) Targeting EphA2 impairs cell cycle progression and growth of basal-like/triple-negative breast cancers. Oncogene 36: 5620-30. PMID: 28581527. PMCID: PMC5629103.
  4. Shiuan, E., Inala, A., Wang, S., Song, W., Youngblood, V., Chen, J., and Brantley-Sieders, D.M. (2020). Host deficiency in ephrin-A1 inhibits breast cancer metastasis. [version 2; peer review: 3 approved]. F1000Research 2020, 9:217 (https://doi.org/10.12688/f1000research.22689.2). PMID: 32399207. PMCID: PMC7194498.

B.  Positions and Honors

Positions and Employment

  • Postdoctoral Fellowship, Vanderbilt University School of Medicine
  • Research Instructor, Vanderbilt University School of Medicine
  • 2006-2015 Research Assistant Professor of Medicine, Vanderbilt University School of Medicine
  • 2015-present Assistant Professor of Medicine, Vanderbilt University School of Medicine

Other Experience and Professional Memberships

1998 Molecular Biology and Pathology of Neoplasia, Edward A. Smuckler Memorial Workshop,Keystone, Colorado

1998-present Member, American Association for Cancer Research

2002 Harvard Medical School Department of Continuing Medical Education and Massachusetts General Hospital Department of Radiation Oncology Seventeenth Annual Offering of Critical Issues in Tumor Microcirculation, Angiogenesis, and Metastasis; Biological Significance and Clinical Relevance Workshop, Cambridge, Massachusetts

2005 National Cancer Institute (NCI)-sponsored Organotypic Models Training Program; received training in orthotopic tumor cell transplantation in mice within several organs, including mammary gland fat pad, bone, lung, spleen, pancreas, bladder, and cecum in the laboratory of Dr. Isaiah J. Fidler, MD Anderson Cancer Center, Houston, Texas

2007-present Ad hoc reviewer for Nature, Cancer Research, PLoS One, Oncogene, Clinical Cancer Research, Neoplasia, European Journal of Cell Biology

2009-2016 Peer reviewer Department of Defense Breast Cancer Research Program

2012 Peer reviewer NCI TME study section                      

Honors

1997-1998      Department of Defense Breast Cancer Pre-doctoral Fellowship

1998-1999       Dissertation Enhancement Award, Vanderbilt University Graduate School

1998-1999       Coordinator for Developmental Biology Student Organization, Vanderbilt University

2000-2001       Public Health Service Vascular Biology Postdoctoral Fellowship

2001-2003       American Heart Association Postdoctoral Fellowship

2001-2002       American Heart Association Basic Cardiovascular Science Council

2003      NIH NRSA Postdoctoral Fellowship 1 F32 CA101419-01 (award offered, declined due to overlap with 2003 DOD award)

2003-2006       Department of Defense Breast Cancer Research Program Postdoctoral Fellowship DAMD17-03-1-0379

2006-2011       NCI Mentored Career Development Award K01CA117915

C. Contributions to Science

My early publications from graduate studies directly addressed how signaling pathways that regulate normal mammary epithelial morphogenesis (e.g. NF-kappaB transcription factors) can contribute to hyperplasia, a hallmark of neoplastic transformation. These publications provided the first evidence that NF-kappaB transcription factors are expressed and active in normal mammary epithelium during post-pubertal development, and that IkappaBalpha deletion in mammary epithelium, which promotes constitutive activation of NF-kappaB transcriptional activity, promotes pervasive intraductal hyperplasia in vivo. These studies laid the foundation for investigating the role of these transcription factors in breast cancer, and also provided training for me in animal models and mammary fat pad clearing and transplantation techniques that have formed a cornerstone of my independent research program and contributed to numerous collaborations, including those with Dr. Chen. I served as primary author for each of these studies and independently designed experiments, interpreted data, and prepared the manuscripts for publication. Funding from my Department of Defense Breast Cancer Pre-doctoral Fellowship award supported this work. I also contributed directly to collaborations that led to publication of work related to the role of NF-kappaB transcription factors to development and disease as a part of my graduate studies.

Brantley, D.M., Yull, F.E., Muraoka, R.S., Hicks, D.J., Cook, C.M., and Kerr, L.D. (2000) Dynamic expression and activity of NF-kappaB during post-natal mammary gland morphogenesis. Mech Dev 97:149-55. PMID: 11025216.

Brantley, D.M., Chen, C.-L., Muraoka, R.S., Bushdid, P. B., Bradberry, J. L., Kittrell, F., Medina, D., Matrisian, L. M., Kerr, L.D., and Yull, F. E.  (2001) Nuclear factor-kappaB (NF-kappaB) regulates proliferation and branching in mouse mammary epithelium. Mol Biol Cell 12: 1445-55. PMID: 11359934. PMCID: PMC34596.

Bushdid PB, Brantley DM, Yull FE, Blaeuer GL, Hoffman LH, Niswander L, Kerr LD. (1998) Inhibition of NF-kappaB activity results in disruption of the apical ectodermal ridge and aberrant limb morphogenesis. Nature 392: 615-8. PMID: 9560159.

I continued to pursue the connection between signaling pathways that regulate development and contribute to tumorigenesis and progression during my post-doctoral training, providing the first evidence that EphA2 receptor tyrosine kinase regulates angiogenesis and tumor neovascularization. These publications showed that EphA2 regulates endothelial cell assembly and motility through a PI3K/Rac1-GTPase-dependent mechanism and regulates tumor angiogenesis in cooperation with the VEGF signaling pathway in vivo, providing novel insight on the molecular regulation of tumor angiogenesis and host-tumor interactions. I served as primary author for each of these studies and independently designed experiments, interpreted data, and prepared manuscripts for publication. Funding from my American Heart Association and Department of Defense Breast Cancer Postdoctoral Fellowship awards supported this work.

Brantley, D. M., Cheng, N., Thompson, E. J., Lin, Q., Brekken, R. A., Thorpe, P. E., Muraoka, R. S., Pozzi, A., Jackson, D., Lin, C., and Chen, J.  (2002). Soluble Eph A receptors inhibit tumor angiogenesis and progression in vivo.  Oncogene 21: 7011-26. PMID: 12370823.

Brantley-Sieders, D. M., Caughron, J., Hicks, D., Pozzi, A., Ruiz, J. C., and Chen, J. (2004). EphA2 receptor tyrosine kinase regulates endothelial cell migration and vascular assembly through phosphoinositide 3-kinase-mediated Rac1 GTPase activation.  J Cell Sci 117: 2037-49. PMID: 15054110.     

Brantley-Sieders, D.M., Fang, W.B., Hicks, D.J., Zhuang, G., Shyr, Y., and Chen, J. (2005) Impaired tumor microenvironment in EphA2-deficient mice inhibits tumor angiogenesis and metastatic progression. FASEB J 19: 1884-6. PMID: 16166198.

Brantley-Sieders, D.M., Fang, W.B., Hwang, Y., Hicks, D., and Chen, J. (2006) Ephrin-A1 facilitates mammary tumor metastasis through an angiogenesis-dependent mechanism by EphA2 receptor and Vascular Endothelial Growth Factor (VEGF) in mice. Cancer Res 66: 10315-24. PMID: 17079451.

As PI or co-investigator on several university- and NIH-funded grants, I laid the groundwork for an independent research program by showing that (1) EphA2 receptor tyrosine kinase is necessary for normal mammary epithelial morphogenesis, (2) EphA2 receptor tyrosine kinase promotes mammary tumorigenesis and metastasis in vivo in HER2-dependent models of breast cancer through physical and functional interaction with HER2 and activation of Ras/Erk and RhoA signaling, and, (3) demonstrating clinical relevance of these observations by interrogating patient mRNA datasets and human tissue microarrays to show that high levels of EphA2 correlate negatively with overall and recurrence-free survival in human breast cancer across multiple subtypes.

Brantley-Sieders, D.M., Zhuang, G., Hicks, D., Fang, W.B., Hwang, Y., Cates, J.M.M., Coffman, K., Jackson, D., Bruckheimer, E., Muraoka-Cook, R.S., and Chen, J. (2008) EphA2 receptor tyrosine kinase amplifies ErbB2 signaling, promoting tumorigenesis and metastatic progression of mammary adenocarcinoma. J Clin Invest 118: 64-78. PMID: 18079969. PMCID PMC2129239.

Vaught, D.B., Fang, W.B., Mazerik, J., Chen, J., and Brantley-Sieders, D.M. (2009) Regulation of mammary gland branching morphogenesis by EphA2 receptor tyrosine kinase.  Mol Biol Cell 20: 2572-81. PMID: 19321667. PMCID: PMC2682598.

Brantley-Sieders, D.M., Jiang, A., Sarma, K., Badu-Nkansah, A., Walter, D.L., Shyr, Y., and Chen, J. (2011) Eph/ephrin profiling in human breast cancer reveals significant associations between expression level and clinical outcome. PLoS One 6: e24426. PMID: 21935409. PMCID: PMC3174170.

Zhuang G, Brantley-Sieders DM, Vaught D, Yu J, Xie L, Wells S, Jackson D, Muraoka-Cook R, Arteaga C, Chen J. (2010) Elevation of receptor tyrosine kinase EphA1 mediates resistance to trastuzumab therapy. Cancer Res 70: 299-308. PMID: 20028874. PMCID: PMC3859619.

My independent research career continues to focus on molecular mechanisms that regulate breast tumorigenesis, host-tumor interactions, and metastatic progression in clinically relevant cell culture and in vivo models. Work initiated in my mentor’s laboratory and supported by an NCI K01 Career Development Award pioneered a role for angiocrine factors regulated by EphA2 in tumor cell growth and invasion in culture and in vivo, providing the first evidence that inhibition of the tumor suppressive angiocrine factor, Slit2, by EphA2 receptor tyrosine kinase promotes tumor cell proliferation and invasion. These studies became the basis of my first independent NIH/NCI R01 grant (CA148934) and publications dissecting the molecular mechanisms through which EphA2 receptor and ephrin-A1 ligand cooperate with VEGF and Slit2 to modulate normal vascular remodeling and tumor angiogenesis in vivo. I served as primary author for the first study and senior author/PI for subsequent studies. I have also recently initiated a collaborative investigation of the role of Rictor/mTORC2 in mammary epithelial morphogenesis and breast cancer with Dr. Rebecca Cook.

Youngblood, V.Y., Wang, S., Song, W., Walter, D., Hwang, Y., Chen, J., and Brantley-Sieders, D.M. (2015)Elevated Slit2 activity impairs VEGF-induced angiogenesis and tumor neovascularization in EphA2-deficient endothelium. Mol Cancer Res. 13:524-37. PMID: 25504371. PMCID: PMC4416411.

Morrison, M.M., Young, C.D., Wang, S., Sobolik, T., Sanchez, V.M., Hicks, D.J., Cook, R.S., Brantley-Sieders, D.M. (2015) mTOR directs breast morphogenesis through the PKC-alpha-Rac1 signaling axis. PLoS Genet 11: e1005291. doi: 10.1371/journal.pgen.1005291. eCollection 2015 Jul. PMID: 26833123. PMCID: PMC4873477.

Morrison-Joly, M., Hicks, D.J., Jones, B., Sanchez, V., Estrada, M.V., Young, C., Williams, M., Rexer, B.N., Sarbassov, D.D., Muller, W.J., Brantley-Sieders, D., and Cook, R.S. (2016) Rictor/mTORC2 drives progression and therapeutic resistance of HER2-amplified breast cancers. Cancer Res 76:4752-64. PMID: 27197158.

In addition to the contributions described above, with a team of collaborators, my experience in manipulation of the mouse mammary gland, including xenograft/allograft models, has directly promoted numerous studies elucidating the molecular mechanisms that regulate breast cancer growth/survival, metastatic progression, and host-tumor interactions. Moreover, these studies have benefitted the community at large (e.g. 2012 PLoS One community profiling study provided data for resource allocation requests by Susan G. Komen for the Cure Middle Tennessee Affiliate) and have forged collaborations that will be key in developing new research directions. I served as a collaborator on these studies, contributing to experimental design, interpretation of data, and manuscript preparation/application for funding (some projects).

Takahashi, K., Sumarriva, K., Kim, R., Jiang, R., Brantley-Sieders, D.M., Chen, J., Mernaugh, R.L., and Takahashi, T. (2016) Determination of the CD148-interacting region in thrombospondin-1. PLoS One 11: 5):e0154916. doi: 10.1371/journal.pone.0154916. eCollection 2016. PMID: 27149518. PMCID: PMC4858292.

Young, C.D., Zimmerman, L.J., Hoshino, D., Formisano, L., Hanker, A.B., Gatza, M.L., Morrison, M.M., Moore, P.D., Whitwell, C.A., Dave, B., Stricker, T., Bhola, N.E., Silva, G.O., Patel, P., Brantley-Sieders, D.M., Levin, M., Horiates, M., Palma, N.A., Wang, K., Stephens, P.J., Perou, C.M., Weaver, A.M., O’Shaughnessy, J.A., Chang, J.C., Park, B., Liebler, D.C., Cook, R.S., and Arteaga, C.L. (2015) Activating PIK3CA mutations induce an EGFR/ERK paracrine signaling axis in basal-like breast cancer. Mol Cell Proteomics 14: 1959-76. PMID: 25953087. PMCID: PMC4587316.

Stanford, J.C., Young, C., Hicks, D., Owens, P., Williams, A., Vaught, D.B., Morrison, M.M., Lim, J., Williams, M., Brantley-Sieders, D.M., Balko, J.M., Tonetti, D., Earp, H.S. 3rd, and Cook, R.S. (2014) Efferocytosis produces a prometastatic landscape during postpartum mammary gland involution. J Clin Invest 124: 4737-52. PMID: 25250573. PMCID: PMCID: PMC4347249.

Brantley-Sieders DM, Fan KH, Deming-Halverson SL, Shyr Y, Cook RS. (2012) Local breast cancer spatial patterning: a tool for community health resource allocation to address local disparities in breast cancer mortality. PLoS One 7:e45238. PMID: 23028869. PMCID: PMC3460936.

Complete List of Published Work in MyBibliography:

*Gap in publications 2018-2019 due to personal breast cancer diagnosis and medical leave.

D.  Research Support

Ongoing Research Support

NIH/NCI (Multi-PI Duvall, Brantley-Sieders, Cook)                                                                07/01/2018-06/30/2023

5R01CA224241

NextGen RNAi delivery to breast tumors for selective mTORC2 blockade.

The goal of this study is to optimize advanced nanocarrier technologies for application to targeting the conventionally undruggable cancer driver mTORC2  in breast cancer, including the impact of systemic rictor-targeting RNAi delivery, alone or in combination with chemo and molecularly targeted therapies, on tumor growth/survival, progression, metastasis, and the tumor microenvironment.

Role: Multi-PI with Craig Duvall and Rebecca Cook – no overlap

Completed Research Support

5K01 CA117915 (Brantley Sieders)                                                                                            07/14/06-06/30/11                                 

NIH/NCI                                                                                                        

The Role of EphA2 Receptor Signaling in Host-Tumor Interactions

The goal of this study is to determine if native, membrane tethered ephrin-A1 ligand activates endothelial expressed EphA2 RTK, linking specific domains of the receptor to initiation of endothelial cell migration and neovascularization.

Role: PI

3K01 CA117915-S1   (Brantley-Sieders) 07/01/09-06/30/11                                         

NIH/NCI                                                                     

The Role of EphA2 Receptor Signaling in Host-Tumor Interactions

Role: PI

NIH/NCI          (Brantley-Sieders)  04/01/2011-03/31/2017

5R01 CA148934

EphA2 receptor in endothelial cell-mediated tumor progression

The goal of this study is to determine how angiocrine factors secreted by tumor endothelilum enhance tumor cell growth and motility, as well as angiogenesis.

Role: PI

NIH/NCI          (Chen and Brantley-Sieders)  07/14/2014-05/31/2019

5R01CA177681

Ephrin-A1 in lipogenesis and breast cancer metastatic progression

The goal of this study is to determine how ligand-independent signaling of EphA receptors in the absence of eprhin-A1 promotes HER2-dependent breast tumor progression, metastasis, and lipid metabolism.

Role: Co-PI with Jin Chen – no overlap

Lumpectomy versus Mastectomy – I’ve had ’em both and I’m telling you all about it!

When you’re diagnosed with breast cancer, no matter what stage or subtype, odds are you’ll be looking at surgery as part of your treatment plan. Got a tumor in your boob? Gotta have it cut out. Thankfully, patients have options when it comes to surgery, and, this is important…

THERE ARE NO RIGHT OR WRONG CHOICES – ONLY INFORMED CHOICES.

Whew, now that I got that off my chest (see what I did there?), let’s talk about two of those surgical options: lumpectomy and mastectomy (single mastectomy in my case, though many women opt for a double mastectomy and that’s okay). A lumpectomy involves removal of the tumor and surrounding tissue while preserving the rest of the natural breast tissue. A mastectomy is complete removal of breast tissue, leaving only skin and the underlying chest muscle behind. I’ve had both, so I speak from personal experience as well as through the lens of science. Here’s the scoop:

In 2018, I opted for a large lumpectomy followed by oncoplastic reconstruction. I’ll blog more about reconstruction options later, but oncoplasty refers to a breast reduction and lift. My tumors were small, I was early stage, and was a great candidate for this less invasive, breast conserving surgery. Even though I was later diagnosed with residual disease, I regret nothing. I simply got unlucky, and mastectomy was always an option if I had recurrence just as it was an option when I was diagnosed with residual disease.

In 2020, when we detected a pesky little 6 mm tumor that didn’t show up the first time, I opted for a mastectomy for the left breast. I chose this so I could maintain sensation on my right side. This was a personal choice – again, no right or wrong choices, only informed choices. I have the same risk of developing cancer in the right breast as I always had (no additional risk by having it in my left breast), and for me, being able to feel touch on the right side was important. Plus, as this 2017 article notes, “Contralateral prophylactic mastectomy (taking off both breasts including the one without cancer) is becoming increasingly common in the United States, and patients considering this option must be counseled about its lack of a survival benefit, its higher complication rate, and the fact that it is risk-reducing but not risk-eliminating.

Before getting into the nuts and bolts, what are the outcome data for lumpectomy versus mastectomy? Breastcancer.org cites a 2014 article from JAMA Surgery, summarizing the data as follows:

From: Breastcancer.org

When combined with radiation, patients who opted for lumpectomy had outcomes that were comparable (even slightly better on average) than patients who opted for mastectomy. Bottom line – for early stage disease, outcomes are comparable for breast conserving surgery versus breast removal.

*Disclaimer – ALWAYS ask your doctor about outcomes and survival odds for your specific breast cancer type, stage, and grade.

Photo source here.

For the lumpectomy, my surgeon removed my tumors and surrounding tissue. Before that, my tumors were marked with Savi Scout devices, radar locators inserted into my left breast with GIANT FUCKING NEEDLES THE SIZE OF SCREWDRIVERS WHILE MY LEFT BOOB WAS IN MAMMOGRAM COMPRESSION. Yes, this is horrifying, but it’s waaaaay better than wire localization, having ACTUAL WIRES STICKING OUT OF YOUR BOOBS to help the surgeon find the target area. After my breast cancer surgeon cut out the tumor, my plastic surgeon took over to perform a reduction (cutting out tissue on both sides) and lift (cutting around my nipples and jacking them up along with the attached breast tissue and stitching the whole thing up in what I like to call an “anchors away” pattern.

Photo credit source.

For my mastectomy, which was a skin and nipple-sparing procedure, my surgeon cut out all of my breast tissue except for a small portion underneath the skin that contains blood vessels necessary to sustain the remaining skin. The point is to de-epithelialize (fancy term for getting rid of the glandular epithelium that is the source of breast cancer) the tissue to make sure no cancer/pre-cancerous cells are left in the chest area. In many cases, including mine, a tissue expander was implanted between the remaining skin and my chest muscle. After recovery and removal of surgical drains (see below), you go to your plastic surgeon’s office to have a nurse locate the built in port with a magnetic port finder and then stick a GIANT FUCKING NEEDLE into the port to fill it up with saline solution, stretching your skin in preparation for reconstruction. After the final fill, you have to wait THREE MONTHS with a HELLA UNCOMFORTABLE foreign body in your chest before reconstruction. That’s where I’m at right now – waiting for my surgery date.

Pros and cons? If you opt for mastectomy, you can most likely skip post surgical radiation therapy. Radiation therapy sucks! It’s painful, causes fatigue, and it takes several months to fully recover. If you opt for a lumpectomy, your surgical recovery time is much faster! I was up and about within 2-3 weeks after lumpectomy/oncoplastic reconstruction. For my mastectomy on the left side, I was down for the count for 6 weeks and not really back to myself until after 8 weeks and completing physical therapy (didn’t need PT with lumpectomy – another advantage). For lumpectomy, I was able to maintain sensation in both breasts/nipples. I could even still feel the one that got nuked (i.e. radiation therapy). For my mastectomy, sensation on the left side is all gone and most likely will never return. Lumpectomy followed by oncoplastic reconstruction gave me a great shape and aesthetic result. My tits were GORGEOUS (as a part of the reconstruction process, I had a reduction and lift on the right breast in order to achieve symmetry)! I went from saggy D cups to very perky, pretty C cups. It was like being 18 again! But, even though the odds were low, I was one of the unlucky patients who had residual disease following lumpectomy and radiation.

Photo source here.

Another consideration – mastectomy required surgical drains. With the removal of tissue and damage resulting from cutting into the body, fluid accumulates in the wounded area and, if undrained, can result in a seroma. To mitigate this complication, the surgeon leaves plastic tubes in the area attached to external suction devices that look like grenades and that need to be emptied several times a day. What comes out ranges from pale liquid to blood red liquid to what I can only describe as “chunky salsa” as pieces of tissue drain out and can sometimes clog the drain and/or the bulb. Yes, it’s that gross. These drains can stay in for up to two weeks, making it impossible to shower, bathe comfortably, exercise, and otherwise operate like a normal, functional human being.

Okay, you CAN function normally, but you’ll fucking pay for it when your drains start filling up faster with bloody, chunky salsa because you overdid it, dumbass. Yeah, I was a total dumbass because “the rules don’t apply to me.”

The rules totally apply to me. Chunky. Salsa.

Photo source here.

And, as noted. spending a minimum of three months with one or two expanders in your body following a mastectomy is a level of sucktastic that I can only describe as follows: I’m kinda like a femebot but without the cool guns. I mean, if you’re going to be a cyborg, you should at least get some cool powers, right? That’s a BIG con when it comes to mastectomy. My oncoplastic reconstruction for lumpectomy happened immediately after my tumor removal surgery, which was super efficient and came with a relatively easy recovery.

Bottom line (louder, for the folks in the back): THERE ARE NO RIGHT OR WRONG CHOICES – ONLY INFORMED CHOICES. Knowledge is power. Get as much information from your healthcare team as possible. Ask questions. Do your research (using reputable sources that cite peer-reviewed data). Ask more questions. You are your own best advocate!

Breast Cancer Care in the Era of Covid-19

It’s been a while! I’ve taken time to recover from my mastectomy (will blog about that later) and, like many folks in self-isolation, I’ve been doing things like gardening, cooking/baking, home improvement, and family activities to fill the time. I waver between being grateful, bored, peaceful, restless, and generally anxious about the immediate and long-term future.

Photo Credit Deposit Photos

And, like many other people battling cancer in the midst of the pandemic, I’ve been dealing with uncertainty about my ongoing treatments on top of the “normal” concerns. I’ll get to my specific case in a bit, but first we’ll go over highlights from a recently published article.

How has cancer care changed in the era of Covid? A recent article from the New England Journal of Medicine provides insight into some of the challenges for breast cancer care. The article is part case study and part discussion of alternative approaches to cancer care designed to mitigate risks of cancer patient exposure to SARS-CoV-2 in healthcare settings. These include delays in surgical tumor removal in some cases where rapid growth/progression of the tumor isn’t a significant risk. One interesting approach is the use of neoadjuvant (a fancy term for treatment before surgery) endocrine therapy (a fancy term for use of estrogen hormone blocking agents like tamoxifen and aromatase inhibitors). As discussed in the article, the advantages of this approach for hormone receptor positive breast cancer include: 1) shrinking the tumor before surgery and improving chances of getting clear margins (no extra tumor left behind after surgery); 2) making breast conserving surgery a safer and more aesthetically pleasing option; 3) giving more time for genomic testing (e.g. OncoType DX – will blog about this later, too) results to come back; 4) determining sensitivity of the patient’s tumor to estrogen suppression, which can also help with the decision whether or not to add chemotherapy.

Photo credit Deposit Photos

The downside, of course, is that delayed surgery and neoadjuvant endocrine therapy require more monitoring (examination, imaging, biopsy, etc.), which takes place in healthcare settings and increases the risk of exposure to the virus. With chemotherapy, which targets rapidly dividing cancer cells (along with hair follicles, cells lining the gut, and immune cells), the risks for exposure to coronavirus is especially problematic as patients are rendered immunocompromised (unable to fight off infections with the body’s natural defenses) or immune fragile (less able to fight off infections). Approaches to mitigate these risks are discussed in the article for hormone receptor positive breast cancer as well as HER2+ and triple negative subtypes. It also discusses ways healthcare providers can and should effectively communicate with patients about treatment decisions and risk management.

Communication – this is an ongoing issue with my care. There are many factors, not the least of which is Covid-19, but we’ve had some…confusion about the schedule for reconstruction following my mastectomy (Note: the surgical team managing my case are PHENOMENAL at what they do, but in both cases, communication with me has not been on par with their skills). When we first scheduled the mastectomy, we also discussed which option might be best for reconstruction and settled on a TUG flap autologous reconstruction. This will involve using a flap of skin, fat, muscle (transverse upper gracilis), and blood vessels from the upper thigh is used to reconstruct the breast. It is a rather involved surgery, which includes microsurgery to reattaches the blood vessels of the TUG flap to the blood vessels in the chest. The nature of the grafting procedure means close monitoring to make certain the graft has sufficient blood flow to survive and thrive, and therefore requires a one night stay in the ICU.

An ICU stay in the era of Covid-19 is a risky and scary prospect!

Because of the risks, my plastic surgeon called and suggested we postpone reconstruction (could have theoretically been done immediately after mastectomy) to minimize the risks of exposure to the coronavirus. That made perfect sense and I agreed. During this conversation, he mentioned reconstruction 6-8 weeks following mastectomy (scheduled for May 11 – meaning reconstruction around June 22 – July 6).

This did not happen. I *think* what happened was a change in timeline due to the need for an expander implant after surgery – this serves as a temporary, fillable implant that can stretch the skin in preparation for reconstruction. I had a skin/nipple sparing mastectomy (glad the nip made it – it was dicey for a week or so), and the expander sat underneath the skin. With an expander, weekly injections into the port with saline gradually increases tension on the skin and stretches it. When I first started expansion, there was talk from the doctor about reconstruction in August.

This did not happen. I *think* it’s because the doctor forgot to let me know that there’s a three month waiting period between the last expansion and reconstruction. Right now, as far as we know, I’m looking at reconstruction around the end of September/beginning of October.

I hope this happens. Again, healthcare providers and patients must be flexible during the pandemic. I trust that my team will make the safest decision about reconstruction.

I just kind of hope they keep me in the loop!

Covid-19 and Cancer – Self-Isolation Isn’t Just About You

On this, my second “Cancerversary,” I want to urge my fellow citizens to take this pandemic seriously, shelter-in-place, flatten the curve, and listen to scientists and health experts rather than politicians and rabble-rousers who value the economy over health and safety.

I originally submitted this as an Op-Ed to several news outlets, but in light of my upcoming surgery, the first of two thanks to Covid-19 dangers that have delayed my reconstruction following mastectomy, I decided to do a blog post. This is important. We’re all in this together, and those who choose to ignore expert advice are putting people like me in danger.

This isn’t the time to be selfish. Self-isolation isn’t just about you.

Like many Americans, I’ve been working remotely to comply with social-distancing and shelter-at-home measures. As a biomedical research scientist, I understand the particularly insidious way SARS-Cov-2, the coronavirus behind the deadly pandemic, can be transmitted exponentially through populations. Death tolls are rising. We’ve been told we need to flatten the curve, which means we need to slow the spread of the virus so we do not exceed the capacity of the healthcare system to treat severely affected patients. There are a limited number of ventilators available, a message that was driven home by Dr. Emily Porter, board-certified emergency physician and sister of U.S. Representative Katie Porter. Dr. Porter used her sister’s approach to educate the public on how exponential spread of the virus could overwhelm the U.S. Healthcare system, forcing doctors to ration resources and decide who gets a vent and who doesn’t. It’s a horrifying, ugly scenario with 1 patient in 50 getting a vent, and 49 patients left to die.

What will happen if we don’t flatten the curve and instead overwhelm the healthcare system.

Her words at sent chills down my spine. “Imagine if you had to say, ‘Oh, I’m sorry. You’ve had cancer before, so therefore you don’t have a perfectly clean bill of health, so you’re not worth saving.’” I am a person living with cancer. My surgery has already been postponed due to the pandemic. Luckily, my tumor is slow-growing, giving me the luxury of time. Many thousands of other Americans and cancer patients around the world do not have that luxury. Cancer treatments cannot be suspended during the pandemic. As I passed through the Vanderbilt-Ingram Cancer Center on my last day of work, I saw a room full of men, women, and children, some in masks, waiting for their chemotherapy treatments. On the floor below, others waited for radiation therapy, and in the hospital a block away, cancer patients were recovering from surgery. These people are not only at risk for exposure while at their appointments, they are also immune-compromised or immune-fragile due to their cancer treatments and are less capable of fighting off the virus. To put that in perspective, a portion of the roughly 650,000 cancer patients who receive chemotherapy annually, not counting those receiving radiation therapy or the host of other patients with co-morbidities, are already more vulnerable to covid-19 death. Without ventilators, an unfathomable number of these patients will likely die. If we ration ventilators based on co-morbidities like cancer, I wouldn’t get a vent if I became infected.

I don’t want to die. None of these cancer patients, or patients with co-morbidities like autoimmune diseases, obesity, diabetes, or others want to die. Can you imagine beating cancer only to succumb to a virus, knowing that your fellow humans didn’t care enough to follow measures to flatten the curve and that’s why you can’t get lifesaving ventilation? Imagine your mother, your grandmother, your child, a newborn baby, your best friend, your colleagues, and imagine life without them—knowing they are gone because the people in their communities didn’t care enough to follow the rules.

Until recently, Tennessee has had a subpar response to the pandemic. Nashville has fared better thanks to measures implemented by the mayor, but there are too many state and local communities that aren’t taking this seriously. I implore them and I implore each of you reading this: follow the rules. Social-distance, shelter-at-home, don’t go out unless absolutely necessary, and take precautions when you do. Wash your hands. Hunker down. We can and will get through this, but only if we all do our part. Please do your part so people like me don’t have to die.

Resources for Cancer Patients During Pandemic: American Cancer Society, Immuno-Oncology News, Breast Cancer News

Covid-19 and Cancer: What You Need To Know

Day three of quarantine for me. My institution is doing the right thing by sending us home. Shutting down laboratory research sucks, but by being cautious and practicing social distancing, we will survive, stay healthy, and be able to get back to work after this necessary pause. I’m privileged to have an employer that recognizes the necessity of these measures, and thanks to National Institutes of Health measures, I’ll still be paid. So my plan is to catch up on scientific literature review, write a review paper, and work with my student remotely on her manuscript in preparation.

I also plan to blog, to write, to spread a bit of information, humor, and hope through the Internet to folks near and far, starting with this post. I’ll cover a bit about the science behind the covid-19 virus – the type of virus, its origin, its mode of spread, and its capacity for mutation and formation of unique strains. Then, I’ll provide information and links to resources to help minimize the risk to cancer patients actively recovering from surgery, on chemotherapy and radiation therapy, and the general considerations patients and survivors should consider during this pandemic.

First, some nomenclature (fancy term for naming things): The virus is actually called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), formerly known as the 2019 novel Coronavirus (2019nCoV). The virus causes the Coronavirus Disease 2019 (COVID-19). Covid-19 is used interchangeably by the media and government agencies for both the virus and the disease it causes. It’s related to the SARS-CoV virus that caused severe acute respiratory syndrome in 2002-2003, as well as MERS-Cov (Middle East Respiratory Syndrome). They are a part of the Betacoronavirus genus, which are characterized by a viral envelop and positive-strand RNA. What does that mean?

Transmission electron micrograph of 2019nCoV virus.
Link to source.

Structure: As you can see from the transmission electron micrograph on the left, the virus is round, and its internal contents are surrounded by an envelop. the spiky protrusions sticking out from that envelop are actually proteins. This inspired the name of this type of virus, as these proteins make the virus look like a crown. These proteins include: (1) clusters of the Spike, or S proteins, latch onto a specific protein on the target cell (receptor molecule), and also help the virus fuse to the target cell membrane and become internalized by the target cell; (2) the Membrane (M) glycoproteins are under the spikes, where they help maintain the shape of viral particles and bind to the inner layers of the virus; (3) Lipid (fat) is taken from host cell membranes during previous infections and incorporated into the viral particle; (4) Envelope (E) glycoproteins help assemble new viral particles and help with release and infectious properties of newly-formed viruses; (5) Nucleocapsid (N) proteins that bind and package the RNA genome also help the virus hide from the host immune system. See figures below.

From CDC.

Link to Source.

Viral Replication and Infection: These viruses break the rules of the Central Dogma of Molecular Biology (i.e. genetic information flows from DNA to RNA to protein – see previous post). Their genetic information is stored as RNA, which is normally the intermediate cells use to create proteins from the genes encoded by DNA. This works to their advantage, since they trick the infected host cell into translating viral RNA encoding the structural proteins that protect the virus, as well as protein processing. They also trick the host cell into replicating the viral RNA genome and packaging it into new viral particles that are then released from the cell to infect other host cells, as shown in the figure below. The cell surface receptor for SARS-CoV-2 is angiotensin-converting enzyme 2 (ACE2), which is expressed on, among other cell types, lung epithelial cells.

Link to source.

One of the most insidious things viruses do is adapt rapidly through mutation of their RNA genomes. This property is actually what allowed both the original SARS-CoV coronavirus and SARS-CoV-2 to cross species and become infectious to humans (zoonotic). SARS-CoV-2 may have originated in bats, and likely made the jump to humans in a wet animal market in Wuhan, China where domestic and wild animals were slaughtered for meat on site, allowing blood and meat from multiple species to mingle (some of the first patients were epidemiologically linked to the market in Wuhan – Reference Khan et al. J. Clin. Microbiol. doi:10.1128/JCM.00187-20 – hit me up for PDF since the article is not yet publicly available). Many infected individuals can be asymptomatic (not sick) while spreading the virus, which makes it even scarier (Lai et al., 2020, Journal of Microbiology, Immunology, and Infection, in press – hit me up for the PDF since the article is not yet publicly available).

Symptoms: Quoted from Khan et al. J. Clin. Microbiol. doi:10.1128/JCM.00187-10 “Clinical features associated with patients infected with SARS-CoV, MERS-CoV and SARS-CoV-2 range from mild respiratory illness to severe acute respiratory disease (1, 17). Both MERS and SARS patients in later stages develop respiratory distress and renal failure (1, 17). Pneumonia appears to be the most frequent manifestation of SARS-CoV-2 infection, characterized primarily by fever, cough, dyspnea, and bilateral infiltrates on chest imaging (17). The period from infection to appearance of symptoms varies. Generally, it is thought to be 14 days, however, a research group at Guangzhou Medical University reported the incubation period to be 24 days. In a family cluster of infections, the onset of fever and respiratory symptoms occurred approximately three to six days after presumptive exposure (41).” Testing for SARS-CoV-2 is performed by using reverse transcriptase polymerase chain reaction (RT-PCR) to amplify viral RNA in samples from patient until levels are high enough to detect.

Treatments: The bad news is that there are no effective treatments for SARS-CoV-2 infected individuals, though pre-clinical testing for remdesivir and chloroquine shows promise, and existing anti-viral targeting approaches may warrant testing. Vaccines are being developed, but will likely not be validated and available for several months to over a year. The best strategies include social isolation to prevent spread, and management of symptoms for infected individuals (but perhaps avoid ibuprofen to be safe). Reinfection is also possible.

What does this mean for cancer patients and survivors? People with cancer and people who are in active cancer treatment may be at higher risk for SARS-CoV-2 infection and severity of Covid-19 Respiratory Sydrome. Survivors not currently in treatment should not be at higher risk, but check with your healthcare team about the effects of ongoing systemic therapies and increased risk. The American Society of Clinical Oncology (ASCO) is sharing and updating information for cancer patients on their blog, and their recommendations as of March 18, 2020, include:

  • Be sure to have enough essential medications, both prescription and over-the-counter, to last for up to a month.
  • Create an emergency contact list that includes family, friends, neighbors, and community or neighborhood resources who may be able to provide information or assistance to you if you need it.
  • Finally, if you are scheduled for cancer treatments during the COVID-19 outbreak, have a discussion with your oncologist about the benefits and risks of continuing or delaying treatment.

These are additional measures, and cancer patients should definitely follow the social-distancing, frequent hand-washing, avoidance of touching face (eyes, nose, mouth) with hands, and avoidance of close contact with sick people. They do not recommend face masks as a way to prevent COVID-19. But if you’re sick with a respiratory illness, like flu or COVID-19, wearing a face mask could prevent the illness from spreading to those around you.

Bottom line: Stay in touch with your healthcare team for guidance on how to minimize exposure risk during ongoing cancer treatments, and follow general population guidelines for social-distancing, hand washing, and disinfection. Wishing you all continued health and safety!

Metastasis 101: How Breast Cancers Spread

Metastasis – the spread of cancer from its initial tissue of origin to another part (or parts) of the patient’s body – is deadly. Metastatic disease is, by and large, what kills people with cancer. It is an ongoing challenge for healthcare providers and researchers, and, as you may have guessed, it’s complicated.

But what exactly is metastasis? How does the process work? And why is it so hard to treat? I’ll cover what we know in this blog post, current and emerging therapies, and ongoing research designed to treat metastatic disease and allow cancer patients to survive and thrive by keeping their metastatic tumors at bay.

Here are the basics: tumor cells that have the ability to break away from the primary mass and invade the surrounding tissue can travel through the body via circulation (by entering the bloodstream directly or or by entering lymph nodes and from there, lymph vessels that shunt fluid back into circulation), invade a secondary organ, and begin to grow and form a new mass at the second location.

This isn’t easy for cancer cells to do. One of my grad school professors once referred to metastatic cancer cells as the decatheletes of cancer cells. Losing cell-cell contact with the tumor mass, invading the surrounding tissue, which is often a hostile environment without resources available to the primary tumor mass, is risky. Entering circulation is even more risky. The cells of origin for cancer cells are not normally equipped to withstand shear forces produced by flowing blood. They also have to avoid detection and destruction by immune cells, not only in circulation, but within the tissue of origin and within lymph nodes. Immune cells are programmed to seek out and destroy unhealthy cells, which may harbor bacterial or viral pathogens that threaten the body as a whole. Metastatic cells also have to crawl along blood vessel walls or hitch a ride on platelets, surviving in circulation without the resources available within the primary tumor mass.

From Schroeder et al. 2011 Nat Rev Can 12: 39-50.

If the metastatic cells manage to survive breaking away from the primary mass, evade vigilant immune cells, and travel through the harsh environment of the circulatory system, they face the arguably greater challenge of exiting circulation and setting up shop in an entirely different organ system that may or may not be similar to their original home. Think of them as colonists. They need to secure a space to live, gather resources from an unfamiliar landscape by competing with native cells that are better equipped because they belong, and they need to adapt and change the behavioral programs controlled by their genetic instructions in order to grow and establish a new tumor.

For breast cancer cells, common sites of metastasis include liver, lung, bone, and brain. Why those sites? One theory, the “seed and soil” hypothesis, argues that tumor cells are like plant seeds, which travel in all directions but can only live and grow if they land in compatible soil, meaning something about these particular organ environments allows tumor cells to take root. It’s an old theory, first posed by English surgeon Stephen Paget after studying autopsy records of 735 patients who died of breast cancer and spotting patterns.

During the process of invasion and metastatic spread, cancer cells experience a lot of pressures, and combined with a relatively unstable genome (covered in previous post), these pressures select for survival of cells that adapt in a process comparable to evolution by natural selection: cells that survive long enough to divide are more likely to pass favorable traits to their daughter cells. One effect of this process is that tumors formed by metastatic cells are often very different from the primary tumor, making them resistant to the therapies used to treat the primary tumor as well as other treatments. Often, they cannot be removed easily by surgery, are resistant to or quickly become resistant to chemotherapy, radiation, and targeted therapies, and grow at a rate that depletes the patient’s body of life-giving resources and causing the organs in which they are lodged to fail. In a nutshell, metastatic disease is incredibly difficult to treat.

So what can we do about it? The good news is that it is possible to manage metastatic disease in some cases, allowing patients to live longer with better quality of life. More therapies are extending the lives of patients living with metastatic breast cancer, including CDK inhibitors like Palbociclib [Ibrance; other similar drugs include Abemaciclib (Verzenio), palbociclib (Ibrance) and ribociclib (Kisqali)] that target cyclin dependent kinases that drive rapid proliferation of cancer cells, slowing their growth. Others include HER2 antibody-chemotherapy drug conjugates (delivers chemotherapy more specifically to HER2+ metastatic breast cancer cells), second-line HER2 targeted therapies, PI3-kinase inhibitors (which target a signaling pathway that is aberrantly activated in ~60% of cancers), PARP inhibitors (block DNA damage repair pathways to make cancer cells respond better to DNA damage inducing chemotherapy), and immune checkpoint inhibitors (activates T-cells in tumors and allows them to kill metastatic tumor cells) among others. See previous post for information about some of these molecular targets. For more on tumor immunology, click here.

These therapies extend the lives of metastatic breast cancer patients, but they are still a temporary fix. As mentioned above, metastatic tumor cells are tough, incredibly adaptable, and able to develop resistance to therapy. Another approach involves finding a way to induce or maintain tumor dormancy, a state in which tumor cells survive but remain quiescent rather than growing rapidly. Many metastatic lesions can persist in a state of dormancy for decades, and we do not yet understand what keeps them dormant, and perhaps more importantly, what activates their growth. But as researchers unravel the molecular mechanism that regulate dormancy and reactivation, new therapies can be developed to maintain dormancy – thus allowing cancer patients to survive and thrive during a normal lifespan in spite of their tumor burden.

Take home message: metastasis is a complex process that enables invading tumor cells to break away from the primary tumor, travel through the patient’s body, and set up shop in different organs. They are difficult to treat and are the main cause of cancer deaths, but current and emerging therapies to manage metastatic cancer are allowing patients to live longer, better quality lives.

For more information: breastcancer.org, Susan G. Komen for the Cure, and the American Cancer Society

Nice Going, AACR (Salt on the Wound)

I didn’t plan on writing two blog posts in one day, but here we are. Because of my second diagnosis with breast cancer, I have to adjust my life and schedule to accommodate surgery, reconstruction, and other treatments. I had planned to attend the annual American Association for Cancer Research Annual Meeting in April so I could present my research on molecular regulation of breast cancer bone metastasis, network with colleagues, patients, survivors, and policy makers, and learn about the latest advances in the field.

Cancer has robbed me of that opportunity.

Since I’d already registered, I contacted AACR to let them know what was going on and to cancel my registration. Here’s what I wrote:

Short, sweet, to the point. I didn’t expect a reply until next week, but, to my surprise (and based on the tone of the reply, horror), I received a reply within a few hours:

So, after writing the American Association for CANCER Research to let them know that I cannot attend the meeting because I have CANCER, that’s the stone cold, insensitive, shitty reply I received. I could’ve let it slide, but, as I note in my response, I’m soooooooo done with bullshit at this point.

Here’s my reply (copied and pasted since it’s too long for a screenshot):

Dear David,


Wow. Just wow.


Two years ago, I would have just let this slide, been “nice” and “quiet” without causing trouble, like all women are taught to do. But two years ago, I was diagnosed with breast cancer. And, as of last week, my breast cancer is back. As such, I have neither the time nor the energy for bovine fecal material. That the current bovine fecal material is coming from the American Association for Cancer Research, an organization I’ve supported since my days as a graduate student (member 1998-present), just after a second diagnosis with breast cancer, makes it all the more horrible.


As I noted in my request, I have cancer. I will likely be undergoing surgery for the third time during the annual conference, which means cancer has cheated me of the opportunity to present my own research findings on breast cancer metastasis to my peers. Cancer will also steal time from my research, my family, my friends, and my life. 
So, in response to, “Please let us know if you still wish to cancel your registration,” um, yeah. Did you think I’d suddenly change my mind, or that my cancer would suddenly be all better so I can totally go to the meeting – my bad? What kind of stupid, insensitive question is that? Seriously, I have people who despise me who wouldn’t be that stone cold. Do you need proof of my diagnosis? I have CDs full of scans from my six biopsies and two lumpectomies. Do I need a doctor’s note? You can check out my blog where I’ve been documenting my story in an effort to let patients going through the same struggles that (a) they’re not alone, (b) knowledge is power so here are accessible data you can use to make informed healthcare decisions, and (c) to be a liaison between research and patients/survivors so the public understands how important our work is and so they’ll engage to help us better meet their needs. www.talkingtatas.com.

You’d best believe I’ll be blogging about the AACR responding to the news that I have cancer and cannot attend the annual meeting with it’ll cost you $125. No “I’m so sorry for what you’re going through.” No, “What can the AACR do to support you during this difficult time.” Just, “We can understand your concern.”


You can understand my concern, you say. With all due respect, no, unless you’ve had cancer, you absolutely, positively cannot understand even a fraction of my concerns. Unless you’ve been hit by the sledgehammer of shock upon hearing those three horrible words, you have cancer, unless you’ve had to tell your spouse, your children, and your mother that you’ve been diagnosed with a deadly disease, unless you’ve endured the pain of surgery and recovery, the burns and fatigue induced by radiation, the indignity of estrogen suppression therapies that forever change you and your relationship to your body, unless you’ve endured sleepless nights wondering if you’ll live for another 5 years, 10 years, 15 years, and if/when cancer might come back and kill you, you have NO IDEA about my concerns. That’s completely insensitive, condescending, and wrong on so many levels.


But please, by all means, take the $125. You certainly need it more than I do. I don’t need to think about insurance deductibles, medication, bills to support myself and my family. 

And one last thing – you don’t get to call me “Dana” in a response like the one you offered. It’s Dr. Brantley-Sieders to you.

A little consideration, human decency, and kindness can go a long way. Coldness, disregard, and insensitivity can, too. Badly done, AACR. Badly done.

Photo credit

DIY Therapy for A Geek

I’ve come to terms with the fact that I’m not done with breast cancer yet. But I don’t have to like it, and I don’t have to pretend that I’m entirely okay. I need help. Still in therapy, meeting with my care team on Thursday to come up with a game plan to get rid of this stupid little 6 mm bastard of a tumor, and then meeting with the plastic surgeon the following Monday to discuss Tits 3.0.

It’s a lot. What’s keeping me sane right now, aside from my family, Netflix Comedy Specials, and cat videos on Facebook, is my work. Y’all, I get to kill breast cancer cells ALL THE TIME in the lab. It’s so cathartic and gratifying. I wish with all my heart it was as easy to kill cancer cells in patients as it is in little plastic dishes. It’s not, but what we discover in little plastic dishes could eventually lead to the next cancer therapy.

The message is clear – DIE BITCH ASS CANCER CELLS!

My amazing student, who’s working with cancer cells that are similar to mine (hormone receptor positive), saved a plate for me. Not only did she save a plate, she decorated it with an adorkable “destroy me” tag that made me giggle snort.

I adore her.

Naturally, we decided to video me killing cancer cells.

Videography credit Kalin Wilson

As noted in the video, please for the love of your health, do NOT drink hydrogen peroxide to kill you tumor. It’s #toxic and not in a way that will target your cancer. But, as you can (hopefully) see, it stresses out the cells in the dish, overwhelming their defenses against oxidative stress to the point of death.

But, having the power to kill tumor cells that are similar to those growing in my body helped me on a psychological level. And if any patients or survivors want me to kill cancer cells like yours in the lab, I’m down! Hit me up. I can use chemo drugs, approved and experimental cancer drugs, peroxide, detergents, soda (it totally works), you name it. Let’s get creative!

Advocacy 101 – What I Learned from Training

I learned so many new things today at Patient Advocacy Orientation! My best days are when I’m learning new things. It’s one of the things I love best about being a scientist, and it’s a great foundation upon which to build for my new work as a Patient Advocate.

What exactly are advocates and what do they do? In terms of Research Advocacy Programs, advocates are disease survivors (cancer survivors in my case), caregivers, and members of the community who provide the patient perspective to researchers to help shape the nature and direction of cancer research and patient care. Their role is critical, as they serve as a voice for patients, helping investigators tailor their research with patients concerns in mind – not just in terms of outcomes and sound science, but also in terms patient comfort, respect for patient rights and dignity, and beneficence. This means making sure the goals of research are focused on and aligned with serving patient needs and improving outcomes and quality of life.

This seems pretty intuitive, and I believe most investigators are truly committed and passionate about doing research that will make a difference, be it developing new treatments, better diagnostic tools, reducing side effects of existing treatments, and improving survival and quality of life for patients. I certainly was and am. But most investigators don’t experience what patients do – except in cases like mine where researchers become patients and survivors. My experience certainly changed my perspective, which is why I want to share what I’ve learned with both the research and survivor communities.

That mission became more urgent for me today in the face of some jarring statistics. Tennessee and the surrounding regions have some of the highest cancer death rates in the United States.

Link to source.

Comparing the map above to the map below that shows new cancer cases diagnosed by state, incidence, the frequency with which cancer occurs, doesn’t fully explain higher death rates.

Link to source.

My heart sank when I saw these data, and really drove home my privilege. I am well-educated, have a high socioeconomic status, have access to insurance coverage and some of the best health care available in the United States, and I have inside information based on my work as a breast cancer researcher.

I’m lucky. Far too many of my fellow Tennesseans and Southerners are not. My Institution and Affiliated Cancer Center serve this region. I want to be a part of better serving patients in this region, which will be a HUGE focus of my advocacy work.

What will this work involve? One of the ways I think I can be of use is by helping recruit patients for clinical trials. According to what I learned today, many promising new drugs do not make it through Phase III clinical trial testing* due to failure to accrue enough patients to sufficiently test their effectiveness. That’s such a shame and missed opportunity. Of course, there are many barriers for patient participation in clinical trials – fear/lack of understanding; lack of access due to barriers to travel/transportation, unmet childcare needs, inability to take time off work, etc.; disparities that make minority populations reluctant to participate**. While I am not in a position to combat access to trials, I am in a position to serve as a liaison between patients and clinical researchers accruing patients for trials. I can help educate potential trial participants in the process, assure them of their rights (including the ability to stop participating at any time), alleviate fears through helping patients understand the benefits and how they might be helping a great number of future cancer patients. I am also working with African American advocates and other advocates of color to understand and be sensitive to those communities, their histories, and their needs.

Those needs are great, particularly in terms of breast cancer outcomes. African American women diagnosed with breast cancer have lower overall survival rates compared to white women. Finding out why is crucial for closing the gap. Increasing African American participation in clinical trials is a key part of that process.

Link to source.

For more on cancer disparities across ethnic groups, click here.

Bottom line: I’ve got work to do, and I’m excited to work with my fellow survivors to help patients now and in the future. Interested in becoming an advocate? Here are some resources that can help! My Institution’s Advocacy Resources, How Patient Advocates Help Cancer Research: Expert Q&A, Why Patient Advocacy is Vital.

*I’ll cover clinical trials in more detail in a future post. Click here to learn more now. Phase III trials test drugs that have already been proven safe and promising in terms of effectiveness.

**African Americans remember the horrific abuses perpetrated by scientific investigators, including those in charge of Tuskegee Study of Syphilis – which resulted in hundreds of African Americans being denied treatment in order to study the long term effects of untreated syphilis