Breast cancer is the most common non-skin malignancy among women, with more than 300,000 new cases diagnosed annually in the United States, according to the American Cancer Society. But breast cancer is not a single disease, and oncology is moving away from “one-size-fits-all” treatment. Understanding the different types of breast cancer and their characteristics can help guide decisions about the most appropriate therapy.

Breast cancer usually arises in the milk ducts or glands called lobules that produce breast milk. Ductal carcinoma in situ (DCIS) refers to abnormal cells that have not spread beyond the milk ducts. Many experts consider DCIS—sometimes called Stage 0 breast cancer—a precancerous condition, but it can progress to invasive cancer.  Less common types of breast cancer include inflammatory breast cancer, Paget disease and angiosarcoma.

Breast cancer is classified by the type of receptors on tumors. Around 75% carry estrogen or progesterone receptors. These are known as HR-positive, or more specifically, ER-positive cancer. Around 15% to 20% of breast tumors have high expression of HER2, a protein that spurs cell growth. However, a majority of tumors historically classified as HER2-negative actually have some HER2 receptors, and with more precise testing they are now classified as HER2-low or HER2-ultralow. Triple-negative breast cancer doesn’t express any of these receptors.

Treatment Options

HR-positive and ER-positive breast cancer is treatable with hormone, or endocrine, therapy that lowers production or blocks the action of estrogen, which encourages the proliferation of cancer cells. Medications include aromatase inhibitors that stop most estrogen production, selective estrogen receptor modulators (SERMs), such as tamoxifen, that prevent estrogen from attaching to cancer cells and selective estrogen receptor degraders (SERDs) that break down the receptors. HR-positive breast cancer may also be treated with targeted therapies, such as CDK4/6 inhibitors, that block signaling enzymes that drive cancer growth.

HER2-positive breast cancer is typically treated with targeted therapies that block the HER2 receptor. These include the monoclonal antibody Herceptin (trastuzumab) and antibody-drug conjugates (ADCs), such as Enhertu (trastuzumab deruxtecan), that deliver potent chemotherapy drugs directly to tumors.

Triple-negative breast cancer (TNBC), which lacks targetable estrogen, progesterone or HER2 receptors, is more difficult to treat. However, these tumors may remain susceptible to targeted therapies that interfere with proteins involved in cancer growth and spread, such as the Trop-2-directed ADCs Trodelvy (sacituzumab govitecan) and Datroway (datopotamab deruxtecan). In some cases, TNBC can be treated with checkpoint inhibitors, such as Keytruda (pembrolizumab), which help the immune system fight cancer.

PARP inhibitors, such as Lynparza (olaparib) and Talzenna (talazoparib), may be an option for people with BRCA gene mutations that prevent cells from repairing damaged DNA, a group at high risk for aggressive breast cancer.

Tailoring Treatment

Precision medicine increasing allows treatment to be matched to an individual patient’s cancer. This highlights the importance of genomic testing to determine whether tumors are likely to be susceptible to different medications.

The breast cancer field is currently moving away from routine surgery, radiation and chemotherapy toward frequent monitoring and tailored treatment. This “less is more” approach can often reduce side effects and improve quality of life. This trend is especially apparent for DCIS, with a growing number of experts favoring active surveillance to monitor for progression.

“Current practice may result in the overtreatment of women whose tumors are at low risk of progression, leading to chronic pain, altered body image, reduced quality of life and other side effects that may be avoidable,” says Shelley Hwang, MD, of Duke Cancer Institute, who led the COMET trial comparing immediate surgery versus active monitoring for people with DCIS.

Several new medications for breast cancer have been approved in recent years, and because therapy is continually evolving, it is often possible to move on to new medications if current ones stop working. Options remain limited, however, for TNBC and metastatic (Stage IV) breast cancer. Many clinical trials of novel therapies are underway—ask your care team about studies that might be right for you.

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