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.

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