A Patient Guide to Understanding HER2-Positive Breast Cancer

HER2-positive breast cancer is a type of breast cancer where cancer cells have higher levels of the human epidermal growth factor receptor 2 (HER2) protein. This protein can promote cancer growth but also provides a target for therapies that have improved outcomes for patients across all stages.

What HER2-Positive Means

HER2-positive — or human epidermal growth factor receptor 2 — breast cancer is largely driven by having copies of HER2 on its cell surface which, in turn, acts as an oncogenic driver of the cancer, telling the disease to grow.

“It used to be many years ago that this subtype of breast cancer was actually associated with worse outcomes than all the other subtypes, really because of this powerful driver of cancer cell growth,” Dr. Sarah M. Tolaney of Dana-Farber Cancer Institute explained in an interview with CURE.

However, ongoing research has led to the discovery of game-changing therapies which target HER2, providing patients with improved outcomes.

“Since the introduction of Herceptin, we have seen that outcomes actually become the same as someone who has a HER2-negative cancer, because we're able to really convert that cancer to one that is so much better behaved,” she explained.

Stage 1 HER2-Positive Breast Cancer Treatment

Patients with stage 1 HER2-positive breast cancer often have small tumors that have not spread to lymph nodes.

• Frontline: Surgery followed by chemotherapy with HER2-targeted therapy such as Herceptin (trastuzumab), sometimes combined with Perjeta (pertuzumab).
• Second-line: Alternative HER2-targeted therapies or clinical trial options if cancer persists.
• Third-line and beyond: Advanced HER2-targeted therapies or antibody-drug conjugates, often in clinical trials.

“Not that anyone wants to choose to have a breast cancer — but if you had to pick one, sometimes people think, ‘Well, maybe it's good to think about a HER2-positive one’. [This is] because there are just so many drugs that will shut off that signal to the cancer cell and have dramatically changed outcomes,” Tolaney said.

Stage 2 HER2-Positive Breast Cancer Treatment

Stage 2 tumors are larger or involve nearby lymph nodes.

• Frontline: Neoadjuvant therapy (treatment before surgery) with chemotherapy plus HER2-targeted therapy to shrink tumors and allow physicians to assess response.
• Second-line: Switch HER2-targeted therapies or combination regimens based on response.
• Third-line and beyond: Newer antibody-drug conjugates or clinical trial options for resistant disease.

Stage 3 HER2-Positive Breast Cancer Treatment

Stage 3 is locally advanced cancer that may involve multiple lymph nodes or nearby structures.

• Frontline: Intensive chemotherapy and HER2-targeted therapy before surgery, followed by additional targeted therapy afterward.
• Second-line: Adjust therapy with different HER2-targeted medications if cancer does not respond.
• Third-line and beyond: Novel therapies, antibody-drug conjugates, or clinical trial options.

Metastatic HER2-Positive Breast Cancer Treatment

Metastatic cancer has spread beyond the breast to other organs.

• Frontline: Taxane chemotherapy with Herceptin and Perjeta to shrink tumors, followed by maintenance HER2-targeted therapy.
• Second-line: Enhertu (fam-trastuzumab deruxtecan-nxki) if cancer progresses.
• Third-line and beyond: Xeloda (capecitabine) plus Tukysa (tucatinib) with Herceptin, then Kadcyla (ado-trastuzumab emtansine); clinical trials are also an option.

“Patients, when they're first diagnosed, get Taxol with Herceptin and Perjeta, then after that, go on to Enhertu, then often go on to Tukysa, capecitabine and Kadcyla, and then go from one treatment to the other with, usually chemotherapy and Herceptin,” Tolaney explained. “[However], this algorithm, I think, is going to continue to evolve.”

“There are so many choices and so many new therapies that are being studied in this setting, including multiple new antibody-drug conjugates targeting HER2 with different chemotherapy being delivered. I do expect that we are going to continue to see outcomes continue to improve for our patients, which is really very nice,” she concluded.

Additional Subtypes: Luminal B, HER2-Enriched, HER2-Low, HER2-Ultra Low

Some patients’ tumors may also have hormone receptor involvement, referred to as Luminal B. HER2 expression can vary:

• HER2-enriched: High HER2 activity and may respond strongly to targeted therapies.
• HER2-low or HER2-ultra low: Tumors show some HER2 expression but may require different therapy approaches; new treatments are being studied in clinical trials.

Talking With Your Oncologist About

Treatment choices depend on cancer stage, overall health, and personal preferences. Patients are encouraged to ask questions about therapy goals, side effects and options for clinical trials. Understanding HER2 status helps guide decisions and improves outcomes.

Your personal experience will be unique. By using this information as a foundation for your discussions, you can partner with your oncologist to make the best decisions for your health.

This article is for informational purposes only and is not a substitute for professional medical advice. Please contact your healthcare team with any questions or concerns.

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