You Need a Book, I Need Ideas for this Blog – Let’s Help Each Other Out! Also, Learn About HER2-low Breast Cancer and How It May Be Treated

It’s day 6 of National Breast Cancer Awareness Month. I’m creating a new post every day in the Month of October to spread awareness, information, accessible science, practical advice, and humor. I can write about the science of breast cancer all day, and I’ve got plenty of stories to tell and woo woo bullshit to debunk, but I really want to hear from y’all.

What do you want to know about breast cancer, breast health, breast biology, treatments, surgeries, radiation, or any topic? Want me to investigate something a friend told you would help with your cancer, or some off the wall thing you found on FaceBook? Need resources on getting screening mammograms, including financial assistance, and on getting breast healthcare? Want to see pictures of my cats and hear about how they’ve kept me entertained and happy during my breast cancer years?

Let me know!

I’m a research whore – send me down a rabbit hole and help me find something new! Comment on this post with what you want to know and I’ll select three folks at random to receive a signed copy of Talking to My Tatas, my breast cancer book.

For today’s topic, let’s talk about the DESTINY-4 clinical trial that represents a HUGE advance in breast cancer treatment options for people with HER2-low advanced cancer. As I discussed in my previous post about breast cancer subtypes, HER2+ breast cancers are diagnosed based on how they look under the microscope and if they have extra copies of the gene that makes the HER2 cell surface receptor protein and/or if they express higher than normal levels of HER2, a protein that makes breast cancer cells grow uncontrollably.

Image source here

The standard of care is to classify HER2+ breast cancers as meeting a threshold for HER2 receptor expression. Cancers that express levels of HER2 below that threshold were considered HER2-negative and not treated with HER2 targeted therapies. But people with low levels of HER2 in their breast tumor could still benefit from HER2-targeted therapies. To test that hypothesis, Dr. Shanu Modi, MD, of the Memorial Sloan Kettering Cancer Center led a clinical trial that tested an antibody drug conjugate called Trastuzumab Deruxtecan (T-DXd) to see if patients with HER2-low metastatic breast cancer benefitted from this treatment. This drug consists of trastuzumab, an antibody that binds to HER2 on tumor cells, and a toxic drug that is delivered directly to the tumor by trastuzumab, which kills cancer cells. People who received this drug in the trial lived longer and had a longer time before their cancer progressed compared to patients who received chemotherapy. The drug reduced tumor burden, the amount of cancer in the body. The major side effects of treatment with this drug include heart and lung function issues, which need to be closely monitored in people taking this drug.

Not only do these results provide hope and more treatment options for patients with metastatic breast cancer, they will likely change the way we classify breast cancers by molecular subtype, adding HER2-low to the classification system. Ongoing clinical trials will test this drug on patients with different levels of HER2 expression to determine the range of expression that defines HER2-low tumors likely to respond.

To learn more about Trastuzumab Deruxtecan, visit the National Cancer Institute website. Click here for more information about breast cancer treatment clinical trials.

Breast Cancer Subtypes – Triple Negative Breast Cancer (TNBC)

It’s the fifth day of National Breast Cancer Awareness Month 2022! Quick update from yesterday – my (hopefully) last breast reconstruction procedure went great! I’m home recuperating and enjoying love from my fur babies and my family. I haven’t looked at the result yet, but the left side of my surgical bra looks fuller. Hooray!

Now, back to the subject of breast cancer molecular subtypes! To recap, breast cancer isn’t a single disease. It is a collection of diseases that cause cells in the breast—specifically the cells that produce and deliver milk to nursing infants called epithelial cells—to grow uncontrollably, forming a tumor. Each breast cancer case is as unique as each person, but they can be classified based on similarities in how they look under a microscope (histology) and on the characteristics of their DNA (molecular).

Molecular breast cancer subtypes, which are crucial diagnostic tools used to determine the best and most appropriate course of treatment, include four subtypes recognized by scientists and clinicians based on their expression of hormone receptors (HR) for estrogen and progesterone (ER and PR) and their expression of the cell-surface receptor HER2: Luminal A, Luminal B, HER2-positive, and Triple Negative Breast Cancer TNBC.

ER = estrogen receptor, PR = progesterone receptor, HER2 = positive for the cell surface receptor HER2, Ki-67 = a marker for how fast cancer cells grow, -ve = negative, +ve = positive. Image Credit Here.

Today’s post is all about the triple negative subtype, which do not express hormone receptors for estrogen and progesterone and also do not express express a cell surface protein receptor called HER2. That’s how it got its name, triple negative, because of the three receptors it does not express. These breast cancers have other ways of growing abnormally that don’t involve hormones or HER2, and they tend to grow very fast. For example, some TNBCs have higher higher than normal levels of EGFR receptors, which are in the same cell surface receptor family as HER2. Like HER2, EGFR normally tell breast cells to grow during normal development in puberty. In cancer, these receptors stay active and make breast cells grow when they shouldn’t, which is a key characteristic of breast cancer. Aside from targeting EGFR, a strategy being tested in clinical trials, people with TNBC have fewer treatment options with targeted therapies (therapies that inhibit hormone receptors and HER2) than other subtypes.

Aside from EGFR receptors, what make TNBC cells grow? There are several molecular pathways that become altered in TNBC. These pathways often function in normal breast epithelial cells telling them to grow when appropriate (cell surface receptors like EGFR, FGFR, and CSF1-R). When receptors on the surface of the cell becomes activated, they send signals to the breast cell that tells it to grow, like when your breasts are growing during puberty. Normally, after puberty, the receptor and related receptors are no longer activated and your breast cells stop growing. In breast cancer, your breast cells make too many receptors, which become constantly activated, making your breast cells grow abnormally, which is one hallmark of cancer. If other changes occur in your breast cells to form a cancerous growth, these receptors make the cancer cells grow uncontrollably.

Photo source here.

One interesting characteristic of TNBC is that this subtype often has more interactions with the body’s immune system, meaning that immune cells travel to the tumor, get inside of it, and try to kill cancer cells and eliminate them from the body. Many cancer cells develop defenses against the immune system, using cell surface proteins like PD-1, PD-L1, and CTLA4 to shut down the immune cells. Tumors with lots of immune cells, called immunologically “hot,” may respond well to immune therapies that block the activity of PD-1, PD-L1, and CTLA4. The drug Pembrolizumab, which targets PD-1, is used to treat advanced TNBC. The drug Sacitiuzumab Govitecin was recently approved to treat TNBC. More on that below!

Image Credit Here.

TNBC breast cancer is not as common as HR+ breast cancer, accounting for 15-20% of breast cancers. However, these breast cancers are often more aggressive and faster growing than HR+ breast cancer. They also disproportionately affect younger women and women of African descent. They are diagnosed by a pathologist based on analysis of gene and protein expression if ER, PR, and HER2 present in cancer cells in a biopsy and in the tumor after surgical removal. Low or no expression of these three receptors leads to a diagnosis of TNBC. This type of breast cancer, like most breast cancers, is first treated by surgery to remove the tumor.

Follow-up treatments include chemotherapy, which was the only option for people diagnosed with TNBC for many decades. Recently, drugs developed specifically to treat TNBC have been approved and are being used in the clinic and undergoing additional testing in clinical trials to refine and optimize their ability to work with other drugs to kill more cancer cells. I discussed Pembrolizumab above. Let’s go over a little bit about Sacituzumab Govitecan. This drug binds to the cell surface protein Trop-2. Many TNBCs have higher than normal levels of Trop-2 on the surface of their cells. Sacituzumab Govitecan, approved in April of 2022, as a treatment for metastatic TNBC, is an antibody-drug conjugate that uses the an antibody against Trop-2 to carry a toxic drug directly to breast cancer cells with high levels ofTrop-2, targeting tumor cells and reducing damage to normal cells and tissues.

These treatments reduce the risk of the cancer from coming back, or recurring. They do come with some not-so-great side effects, which your oncologist should consider and help you with. Quality of life should always be a consideration when it comes to cancer treatment.

For more on TNBC, check out the American Cancer Association. As with other subtypes of breast cancer, early detection increases your chance of survival, so keep up with your routine mammograms and self-exams. Though TNBC is trickier to detect, screening mammography remains a vital tool for early detection of TNBC and other breast cancer cell types.

Breast Cancer Subtypes – HER2 positive (HER2+) Disease

It’s the third day of National Breast Cancer Awareness Month 2022! To recap, breast cancer isn’t a single disease. It is a collection of diseases that cause cells in the breast—specifically the cells that produce and deliver milk to nursing infants called epithelial cells—to grow uncontrollably, forming a tumor. Each breast cancer case is as unique as each person, but they can be classified based on similarities in how they look under a microscope (histology) and on the characteristics of their DNA (molecular).

Molecular breast cancer subtypes, which are crucial diagnostic tools used to determine the best and most appropriate course of treatment, include four subtypes recognized by scientists and clinicians based on their expression of hormone receptors (HR) for estrogen and progesterone (ER and PR) and their expression of the cell-surface receptor HER2: Luminal A, Luminal B, HER2-positive, and Triple Negative Breast Cancer.

ER = estrogen receptor, PR = progesterone receptor, HER2 = positive for the cell surface receptor HER2, Ki-67 = a marker for how fast cancer cells grow, -ve = negative, +ve = positive. Image Credit Here.

Today’s post is all about the HER2-enriched (also called HER2+) subtypes, which express a cell surface protein receptor called HER2. These breast cancers have higher than normal levels of HER2 receptors, which normally tell breast cells to grow during normal development in puberty. In cancer, these receptors stay active and make breast cells grow when they shouldn’t, which is a key characteristic of breast cancer. Luminal B breast cancers have too much of the cell surface receptor HER2 in addition to having too much estrogen and progesterone receptors (ER/PR +ve), as do breast cancers that do not also express hormone receptors (HER2-enriched).

How does HER2 receptors make breast cancer cells grow? When the receptor on the surface of the cell becomes activated, it sends a signal to the cell that tells it to grow, like when your breasts are growing during puberty. Normally, after puberty, the receptor and related receptors are no longer activated and your breast cells stop growing. In breast cancer, your breast cells make too many HER2 receptors, becoming constantly activated ,making your breast cells grow abnormally, which is one hallmark of cancer. If other changes occur in your breast cells to form a cancerous growth, these HER2 receptors make the cancer cells grow uncontrollably.

Image Credit Here.

HER2+ breast cancer is not as common as HR+ breast cancer, accounting for 10-20% of breast cancers. However, these breast cancers are often more aggressive and faster growing than HR+ breast cancer. They are diagnosed by a pathologist based on analysis of HER2 gene expression and HER2 proteins present in cancer cells in a biopsy and in the tumor after surgical removal. This type of breast cancer, like most breast cancers, is first treated by surgery to remove the tumor. .

Follow-up treatments include chemotherapy and HER2-targeted therapies that block the activity of HER2 on breast cancer cells, including antibody drugs that bind to HER2 receptors and cause them to be degraded by the cell as well as triggering the body’s natural immune system to attack HER2+ tumor cells. These drugs include Trastuzumab and Pertuzumab. A derivative of Trastuzumab called Ado-trastuzumab emtansine (also called T-DM1) is an antibody-drug conjugate that uses the Trastuzumab antibody to carry emtansine chemotherapy directly to breast cancer cells with high levels of HER2, targeting tumor cells and reducing damage to normal cells and tissues.

These treatments reduce the risk of the cancer from coming back, or recurring. They do come with some not-so-great side effects, which your oncologist should consider and help you with. Quality of life should always be a consideration when it comes to cancer treatment.

For more on HER2+ positive breast cancer, check out the American Cancer Association. As with other subtypes of breast cancer, early detection increases your chance of survival, so keep up with your routine mammograms and self-exams.

Breast Cancer Subtypes – Hormone Receptor Positive (HR+) Disease

It’s the second day of National Breast Cancer Awareness Month 2022! Did you know that breast cancer isn’t a single disease? It is a collection of diseases that cause cells in the breast—specifically the cells that produce and deliver milk to nursing infants called epithelial cells—to grow uncontrollably, forming a tumor. Each breast cancer case is as unique as each person, but they can be classified based on similarities in how they look under a microscope (histology) and on the characteristics of their DNA (molecular).

This post and upcoming posts will focus on molecular breast cancer subtypes, which are crucial diagnostic tools used to determine the best and most appropriate course of treatment. There are currently four molecular breast cancer subtypes recognized by scientists and clinicians based on their expression of hormone receptors (HR) for estrogen and progesterone (ER and PR) and their expression of the cell-surface receptor HER2: Luminal A, Luminal B, HER2-positive, and Triple Negative Breast Cancer.

ER = estrogen receptor, PR = progesterone receptor, HER2 = positive for the cell surface receptor HER2, Ki-67 = a marker for how fast cancer cells grow, -ve = negative, +ve = positive. Image Credit Here.

Today’s post is all about Luminal A and Luminal B subtypes, which are hormone receptor-dependent (hormone receptor-positive, also known as estrogen receptor-positive or estrogen receptor/progesterone receptor-positive). These breast cancers have higher than normal levels of receptors for estrogen (ER+) and progesterone (PR+), which normally tell breast cells to grow during pregnancy as they get ready to start producing milk. In cancer, these receptors stay active and make breast cells grow when they shouldn’t, which is a key characteristic of breast cancer. Luminal B breast cancers also have too much of the cell surface receptor HER2, which also makes breast cells grow uncontrollably, contributing to cancer. HER2 positive breast cancer will be covered in the next post.

How do estrogen and progesterone receptors make cancer cells grow? Estrogen produced by your body binds to molecules called receptors. When estrogen or progesterone enters a breast cell, it binds to a partner, called a receptor. When the receptor binds to the hormone, it sends a signal to the cell that tells it to grow, like when you’re pregnant and your breasts are getting ready to make milk for when the baby is born. Normally, after pregnancy and lactation, estrogen levels in your body go down and your breast cells stop growing. In breast cancer, your breast cells make too many receptors, so when estrogen levels go up in your body, like during your normal menstrual cycle, your breast cells grow abnormally, which is one hallmark of cancer. If other changes occur in your breast cells to form a cancerous growth, these estrogen and progesterone receptors make the cancer cells grow uncontrollably.

Image Credit Here.

Hormone receptor positive, also referred to as ER+, ER/PR+ breast cancer, is the most common type of breast cancer, accounting for 70-80% of breast cancers. They are diagnosed by a pathologist based on analysis of hormone receptor proteins present in cancer cells in a biopsy and in the tumor after surgical removal. This type of breast cancer, like most breast cancers, is first treated by surgery to remove the tumor. Depending on stage and grade, the ER/PR+ breast cancers should be analyzed by tumor genomic tests like Oncotype Dx or MammaPrint, which helps predict how likely the cancer is to recur (i.e. come back) and if chemotherapy is necessary for treatment.

Follow-up treatments include hormone therapies that block the activity of estrogen in the body, like the drug Tamoxifen, drugs that block estrogen production by the body, aromatase inhibitors like Letrozole, Arimidex, and Exemestane, or drugs that degrade estrogen receptor like Fulvestrant. Other ER+ breast cancer treatments include drugs that block the activity of proteins that drive cell growth (CDK inhibitors), including Ribociclib, Palbociclib, and Abemaciclib. These are typically used in combination with endocrine therapies like Tamoxifen/AIs/Fulvestrant to treat metastatic breast cancer, which has spread to other parts of the body. For women diagnosed with cancer who haven’t yet undergone menopause, medically induced menopause may be recommended. These treatments reduce the risk of the cancer from coming back, or recurring. They do come with some not-so-great side effects, which your oncologist should consider and help you with. Quality of life should always be a consideration when it comes to cancer treatment.

For more on hormone receptor positive breast cancer, check out the American Cancer Association. As with other subtypes of breast cancer, early detection increases your chance of survival, so keep up with your routine mammograms and self-exams.

Raising Money to Support Breast Cancer Research!

October is Breast Cancer Awareness Month! As a breast cancer researcher and breast cancer survivor, I’m all about giving back and supporting the cause. In that spirit, this year I’m raising money for The American Cancer Society Making Strides Against Breast Cancer Initiative.

A set of Breast Cancer Awareness cards.

Want to help? Donate to my fundraiser and I’ll feature your survival story (or a loved one’s story) on my blog. You can make the donation in honor of someone you love who’s battled breast cancer. My fundraiser is dedicated to my mom, a 10 year survivor, and my cousin, who I lost at the age of 37 to HER2+ breast cancer.

Want something more tangible? Well, my side hustle is writing fiction, including paranormal romance and urban fantasy, which you can read all about at D.B. Sieders. I’m donating all of my royalties from October and November to Making Strides. So you can buy some books, enjoy them, and know that your money is supporting a great cause.

Making Strides Against Breast Cancer

UPDATETeam Lab Rats raised $1,500 for Making Strides! Thank you to everyone who donated, bought my books in October, and for everyone who supported and shared fundraiser deets! I’ll be posting pictures from the event this weekend!

Me The Day Before My Breast Cancer Surgery

I’m thrilled to be a part of the 2019 Making Strides Against Breast Cancer Initiative, sponsored by The American Cancer Society and Avon. American Cancer Society is a great organization, supporting researchers, patients, survivors, and clinicians. I’ve had the great fortune to serve as a peer reviewer for their research grants program, and I’ve got to tell you – there are some AMAZING new investigators across the United States working hard every day to find new treatments, better diagnostics, better interventions, and extending our knowledge of this complex and terrifying collection of diseases.

In addition to research, they fund patient transport to and from treatments, personal assistance to help patients understand their diagnosis and get the help they need, and one-on-one support for breast cancer patients. This is a fantastic organization that I’m proud to support as a researcher, advocate, and survivor.

I’m Team Leader for Team Lab Rats, and we’ve raised over $1,000 so far and growing! I’m also donating 100% of my October book royalties to this Making Strides Fundraiser. Pictures and updates to follow.

If you or someone you love has been diagnosed with cancer, reach out to The American Cancer Society for accurate information, resources, and support. Knowledge is power. You are not alone.