How HER2-Negative Breast Cancer Is Treated

Treating HER2-negative breast cancer and other types of breast cancer may require one or more treatments ranging from surgery and radiation to medications like chemotherapy, hormone or targeted therapy, and immunotherapy.

Several factors are considered when creating a person's treatment plan, including their breast cancer stage (how far their cancer has spread and the amount of cancer) and whether their cancer cells have hormone receptors or large amounts of the HER2 protein.

Human epidermal growth factor receptor 2 (HER2) is a growth-promoting protein found on the surface of breast cells. HER2-negative breast cancers have normal levels of the protein HER2, whereas HER2-positive breast cancers have elevated protein levels.

This article provides insight into how HER-2-negative breast cancer is treated. Complementary treatments and preventive lifestyle strategies will also be reviewed.

Healthcare provider discusses treatment options with person with breast cancer

SDI Productions / Getty Images


Most individuals with breast cancer, including those with HER2-negative breast cancer, have some form of surgery as part of their treatment plan.


A breast surgeon removes the whole breast and surrounding tissues during a mastectomy.

Types of mastectomies include:

  • Simple (total) mastectomy: The surgeon removes all breast tissue from the affected breast.
  • Modified radical mastectomy: The surgeon removes all breast tissue from the affected breast and the underarm lymph nodes.
  • Radical mastectomy: The surgeon removes all breast tissue from the affected breast, the underarm lymph nodes, and the chest muscle beneath the breast. This mastectomy is uncommonly performed and is reserved for individuals with metastatic breast cancer (cancer that has spread to other parts of the body).

Breast Reconstruction

After a mastectomy, a person may desire breast reconstruction by a plastic surgeon. Breast rebuilding occurs during the same mastectomy operation (immediate reconstruction) or after the mastectomy (delayed reconstruction).

Breast-Conserving Surgery

Also called a lumpectomy, breast-conserving surgery involves surgically removing the "lump" of cancerous breast tissue and some surrounding healthy breast tissue. If breast-conserving surgery is chosen, radiation is also usually needed.

Lymph Node Surgery

If breast cancer spreads, it usually goes first to lymph nodes in the armpit (axillary lymph nodes). Lymph node surgery can be done simultaneously with a mastectomy or breast-conserving surgery or during a second operation.

There are two main types of lymph node surgeries for treating breast cancer:

  • Sentinel lymph node biopsy: The surgeon injects a blue dye into the breast tumor and the surrounding area. The surgeon then removes the axillary lymph nodes that take up the dye since these are the areas the cancer is likely to spread to first.
  • Axillary lymph node dissection: The surgeon removes multiple underarm lymph nodes (from 10 to 40).


Radiation therapy involves the use of high-energy rays to destroy cancer cells. A medical doctor called a radiation oncologist administers the treatment.

Radiation is used after breast-conserving surgery to help prevent cancerous cells from returning to the breast or closeby lymph nodes.

It's also used after a mastectomy if the tumor is larger than 5 centimeters (cm) or if cancer cells are found in four or more lymph nodes.

Radiation may also be used to treat individuals with stage 4 breast cancer that has spread to the brain, bones, or spinal cord.

The two main types of radiation used in the treatment of HER2-negative breast cancer (and other types of breast cancer) are:

  • External beam radiation: A machine aims radiation beams at the breast tissue.
  • Brachytherapy (also known as internal radiation): A device containing tiny radioactive seeds or pellets is implanted into the area of the breast where the cancer was surgically removed.

A whole-breast radiation schedule is typically five days a week for five weeks.

Accelerated Partial Breast Irradiation

Due to the time commitment for radiation, accelerated partial breast irradiation (APBI) may be suggested, typically for patients at least 50 years old with small, early-stage breast cancer. With APBI, higher doses of radiation are aimed at a smaller volume of breast tissue over a shorter time.


Different types of medication may be used to treat HER2-negative breast cancer, especially if it's advanced or metastatic.


Chemotherapy (chemo) involves using drugs, typically a combination, to kill fast-growing cancer cells. The drugs are administered in three- to six-month cycles, typically lasting two or three weeks.

Keep in mind that not everyone with HER2-negative breast cancer needs chemotherapy. If you do, you will receive it before or after surgery, depending on factors like the size and extent of your cancer.

Terms used to describe the timing of chemo with regards to surgery include:

  • Adjuvant therapy: This chemo is given after surgery to destroy microscopic cancer cells that may have been left over after the operation.
  • Neoadjuvant therapy: This chemo is given before surgery and generally is reserved for large cancers and/or cancers involving multiple lymph nodes.

Examples of Chemotherapy for Breast Cancer

The two major classes of drugs for breast cancer treatment are:

Hormone Therapy

Hormone therapy is usually taken for at least five years after surgery (and chemotherapy, if given) to help prevent cancer from returning.

It's only recommended for individuals with hormone-receptor-positive breast cancers, in which the cancer cells produce hormone receptors (proteins) that can bind to estrogen, progesterone, or both.

Hormone treatments work by lowering estrogen levels or blocking the action of estrogen.

Some standard hormone therapies used to treat hormone-receptor-positive breast cancer (which can be HER2-positive or HER2-negative) include:

  • Nolvadex (tamoxifen) is a pill that works by blocking estrogen from binding to receptors on cancer cells. This drug is typically the first choice for premenopausal individuals.
  • Aromatase inhibitors (AIs) are pills that prevent the aromatase enzyme from making estrogen in the body.

Targeted Drug Therapy

Targeted drug therapy involves medications targeting and destroying breast cancer cells with specific proteins.

These medications can be given intravenously (given through an IV in the vein), injected under the skin, or taken as a pill. Their side effects are different from that of traditional chemotherapy.

As an example, the drugs Ibrance (palbociclib), Kisqali (ribociclib), and Verzenio (abemaciclib) are approved for people with advanced or metastatic hormone receptor-positive, HER2-negative breast cancer.

These medications are taken as pills and are part of a newer drug class called cyclin-dependent kinase inhibitors. They target proteins involved in breast cancer growth.

Likewise, other targeted drugs Lynparza (olaparib) or Talzenna (talazoparib), may be given to individuals with the BRCA mutation who have metastatic HER2-negative breast cancer. These drugs are pills taken after surgery and chemotherapy. They block PARP proteins, which help repair damaged DNA inside cells.


Immunotherapy uses the body's immune system to manage various diseases. Drugs called immune checkpoint inhibitors can be used to treat certain types of metastatic breast cancer.

What Are Immune Checkpoints?

Immune "checkpoints" are proteins that usually help your immune system distinguish between healthy and dangerous cells. Breast cancer cells can mimic checkpoint proteins to avoid being detected by the immune system.

One IV drug, Keytruda (pembrolizumab), targets a checkpoint protein called PD-1. By blocking PD-1, Keytruda can expose and boost the immune response against breast cancer cells, which can often shrink the cancer.

Keytruda is used with chemotherapy to treat triple-negative breast cancer, which is estrogen receptor-negative, progesterone receptor-negative, and HER2-negative.

Complementary Medicine

Complementary and alternative medicine (CAM) in breast cancer care involves engaging in practices that can help you manage bothersome cancer-related symptoms or treatment-related side effects, like fatigue or poor sleep.

It's important to understand that these practices are done along with your breast cancer treatments. They should never replace standard medical care.

Examples of complementary therapies used in individuals with breast cancer, including HER2-negative breast cancer, are:

  • Yoga: This practice originated in India and combines poses, meditation, and breathing techniques to bring together the body, mind, and spirit symbolically.
  • Reiki: This spiritual healing practice is based on the belief that energy travels through the body. During a Reiki session, a practitioner will place their hands on or just above specific locations on your body to transfer or encourage healthy energy flow.
  • Acupuncture: This is a traditional Chinese healing practice in which sterile, tiny needles are placed into the skin at specific points to channel energy. It may stimulate the nervous system to release natural chemicals.

Complementary therapies may include cannabis products, like cannabidiol (CBD) or tetrahydrocannabinol (THC). These products are derived from the marijuana plant Cannabis sativa.

Remember that while cannabis may help some people ease symptoms like pain or anxiety related to breast cancer or its treatment, cannabis is not a standard treatment or cure for breast cancer.

Talk With Your Healthcare Providers

Before incorporating any complementary therapy into your daily life, be sure to discuss it first with your breast cancer healthcare providers. Some therapies may not be suitable or safe when combined with conventional breast cancer treatments.


You cannot treat breast cancer with lifestyle behaviors. However, you can help prevent breast cancer from returning by adopting these healthy behaviors:

  • Avoid alcohol.
  • Maintain a healthy weight,
  • Eat a low-fat, plant-predominant diet with an abundance of whole grains, fruit, and vegetables.
  • Get 150 to 300 minutes of moderate-intensity or 75 to 150 minutes of vigorous-intensity activity each week. Moderate-intensity activities include brisk walking, water aerobics, or cycling.  


HER2-negative breast cancer is a type of breast cancer that has normal levels of the HER2 protein. The treatment of HER2-negative breast cancer is individualized and depends significantly on factors like cancer size, extent, and hormone status.

Treatment may include a mastectomy or breast-conserving surgery with radiation and medications, like chemo, hormone or targeted therapy, or immunotherapy.

Complementary therapies can help ease cancer-related symptoms but should never replace standard medical care. Likewise, healthy lifestyle habits can help prevent breast cancer in the first place (or from recurring) but cannot cure or treat breast cancer.

A Word From Verywell

It's essential to see a healthcare provider if you experience any worrisome breast symptoms, like a new lump, breast swelling, or nipple discharge. This pertains to people of all genders.

If you are female, talk with your healthcare provider about undergoing screening mammograms. A mammogram can detect breast cancer before symptoms arise. If you are transgender, talk with your healthcare provider about what screening is recommended for you.

Frequently Asked Questions

  • What is early-stage breast cancer?

    Early-stage breast cancer is cancer that has not spread beyond the breast or underarm lymph nodes.

  • How is early-stage breast cancer treated?

    Treatment of early-stage breast cancer typically entails breast-conserving surgery with radiation or a simple mastectomy. After surgery, hormone therapy with tamoxifen or an aromatase inhibitor may be given if the cancer is hormone-receptor-positive.

  • Is HER2-positive breast cancer more aggressive than HER2-negative breast cancer?

    Generally speaking, yes. HER2-positive breast cancers grow and spread faster and are more likely to come back (recur) than HER2-negative breast cancers.

    That said HER2-positive breast cancers can respond to drugs that target and block the HER2 protein. These drugs include Herceptin (trastuzumab) and Perjeta (pertuzumab).

  • How is metastatic HER2-negative breast cancer treated?

    Metastatic HER2-negative breast cancer is usually treated with medications that can help manage, not cure, the cancer. These may include hormone therapy (if the cancer is hormone-receptor-positive) or chemotherapy.

    Targeted drugs like Ibrance (palbociclib) or the immunotherapy Keytruda (pembrolizumab) may also be considered.

  • Can males get breast cancer?

    Breast cancer is far more common in females, but it can also occur in males. According to the American Cancer Society, there is around a 1 in 833 chance that a male will develop breast cancer in their lifetime and a 1 in 8 chance that a female will.

12 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Cihan YB, Sarigoz T. Role of postmastectomy radiation therapy in breast cancer patients with T1-2 and 1-3 positive lymph nodes. Onco Targets Ther. 2016;9:5587-95. doi:10.2147/OTT.S106871

  2. Radiation therapy.

  3. Dutta SW, Showalter SL, Showalter TN, Libby B, Trifiletti DM. Intraoperative radiation therapy for breast cancer patients: current perspectivesBreast Cancer (Dove Med Press). 2017;9:257-263.  doi:10.2147/BCTT.S112516

  4. American Cancer Society. Chemotherapy for breast cancer.

  5. Cai F, Luis MAF, Lin X, et al. Anthracycline-induced cardiotoxicity in the chemotherapy treatment of breast cancer: preventive strategies and treatment. Mol Clin Oncol. 2019;11(1):15-23. doi:10.3892/mco.2019.1854

  6. Willson ML, Burke L, Ferguson T, et al. Taxanes for adjuvant treatment of early breast cancer. Cochrane Database Syst Rev. 2019;9(9):CD004421. doi:10.1002/14651858.CD004421.pub3

  7. Drăgănescu M, Carmocan C. Hormone therapy in breast cancer. Chirurgia (Bucur). 2017;112(4):413-417. doi:10.21614/chirurgia.112.4.413

  8. Lau KH, Tan AM, Shi Y. New and emerging targeted therapies for advanced breast cancer. Int J Mol Sci. 2022;23(4):2288. doi:10.3390/ijms23042288

  9. Wu X, Gu Z, Chen Y, et al. Application of PD-1 blockade in cancer immunotherapy. Comput Struct Biotechnol J. 2019;17:661-674. doi:10.1016/j.csbj.2019.03.006

  10. Complementary therapies.

  11. Mussallem D. Lifestyle for breast cancer risk reduction. Menopause. 2022;29(8):979-981. doi:10.1097/GME.0000000000002006

  12. American Cancer Society. Key statistics for breast cancer.

By Colleen Doherty, MD
 Colleen Doherty, MD, is a board-certified internist living with multiple sclerosis.