Treatment Update: Breast Cancer With Highlights From the 2023 San Antonio Breast Cancer Symposium

Each year in the United States, there are nearly 300,000 diagnoses of breast cancer. In recent years, the number of effective treatments for breast cancer has increased. Breast cancer is not just one disease. There are several different subtypes, each with unique features. Doctors are able to tailor treatments according to the characteristics of these specific subtypes.

Both men and women can be diagnosed with breast cancer, with men representing about 1 percent of all breast cancer cases. Treatment updates often refer only to women patients, but there are risks across other populations, including men and trans women undergoing hormone treatment. This booklet is for anyone facing a breast cancer diagnosis. Your health care team will tailor a treatment plan that best fits your situation.

In this update, we talk about current available breast cancer treatments and new medicines in development. We also describe how to cope with possible treatment side effects and how to communicate most effectively with your health care team.

Types of Breast Cancer

Hormones and other chemical messengers in the bloodstream can attach to specialized proteins (called receptors) and fuel the growth of cancer cells. These receptors may lie within or on the surface of cancer cells.

There are four main subtypes of breast cancer, based on the presence or absence of specific receptors:

Hormone receptor (HR) positive. Cancers that have receptors for estrogen (ER-positive) and/or progesterone (PR-positive) are considered hormone-positive. Nearly two-thirds of ER-positive cancers are also PR-positive.
HER2-positive. This type of breast cancer contains an overabundance of a protein called human epidermal growth factor receptor 2 (HER2). About half of HER2-positive cancers are also HR-positive.
HER2-low. Breast cancers that do not contain an overabundance of the HER2 protein.
Triple-negative (TNBC). Breast cancers that do not have receptors for estrogen or progesterone and do not contain an overabundance of the HER2 protein.

Diagnostic Tests

Mammogram

A mammogram is an X-ray picture of the breast. It is often the first test used to check for breast cancer in those who have a lump or another sign of tumor growth. A mammogram is also used as a screening test when there are no apparent signs or symptoms of breast cancer. If the doctor sees anything suspicious, additional tests are conducted.

Ultrasound

Breast ultrasound uses sound waves to examine the breast. This is another common tool in evaluating breast lumps and other abnormal findings, especially in young patients who have breasts that are considered dense (have a relatively high amount of glandular tissue and fibrous connective tissue and a relatively low amount of fatty tissue).

Magnetic Resonance Imaging (MRI)

Breast MRI uses magnetic waves to evaluate breast tissue and breast abnormalities. For some individuals at high risk of developing breast cancer (such as anyone with strong family histories of breast cancer and/or BRCA or other gene mutations), breast MRI may be recommended as part of cancer screening. Some individuals are candidates for breast MRI for surveillance after they have completed breast cancer treatment.

Biopsy

Tests performed on tumor samples provide doctors with valuable information that helps guide treatment decisions. One such test is a biopsy, in which a doctor uses a needle to remove a tissue sample from the tumor so that it can be examined under a microscope. Some breast biopsies require surgery (known as an excisional biopsy).

Biopsies can help doctors determine whether the tumor is non-invasive (has not spread outside the milk duct or gland, where breast tumors usually begin) or invasive (has spread outside the duct or gland into nearby breast tissue). Another important piece of information that can be learned from the biopsy is the tumor’s hormone receptor status, which indicates whether or not the tumor’s growth is driven by hormones (ER-positive, PR-positive or HER2-positive).

There are also “liquid” biopsies that can be used in the diagnosis of breast cancer. In a liquid biopsy, the DNA that is shed into the blood by breast cancer tumors is collected via a blood test and examined for cancer cells.

Surgical Staging

In a staging surgery, the surgeon removes the tumor to determine the size and microscopic patterns of cancer cells to assess how likely the cancer is to return. The surgeon also removes one or more lymph nodes in the underarm near the affected breast to see if they contain cancer cells. Lymph nodes are part of the immune system and can be one of the first sites where cancer cells spread in cases of early breast cancer.

Genomic Tests

In certain cases of early-stage breast cancer, a test called a “genomic assay” or “gene expression profile” may be used. This test is designed to detect several types of genes or groups of genes in the cancerous cells. The expression profile of these genes can help doctors determine how likely it is that a person with early-stage breast cancer will have the cancer return after completing treatment. (A patient’s recommended treatment is dependent on the type of cancer as well as other factors.) Having certain genes can also be associated with a higher likelihood of the cancer responding well to a particular drug.

Genomic assays provide a quantitative (numbers-based) analysis that can help patients and their doctors better understand the prognosis and decide if additional treatment should be pursued. Commonly used genomic assays include the Oncotype DX score, MammaPrint and others.

Introduction Treatment Options

CancerCare’s Free Support Services and Programs

It can be very difficult to receive a diagnosis of breast cancer, and adjusting to the necessary changes in your life can be challenging.

CancerCare can help. We are a national nonprofit organization providing free, professional services to anyone affected by cancer. Our licensed oncology social workers can provide support and education, help in navigating the complicated health care system, and provide information on support groups and other resources.

To learn more about how CancerCare helps, call us at 800-813-HOPE (4673) or visit www.cancercare.org.

You will likely also build your own personal support network, composed of family and friends. In doing so, it’s best to take some time to think about the people in your life and how they are best suited to help. Match the task to their strengths—ask a family member who loves to shop to pick up something for you at the store; ask a friend who’s a good listener to come over for a chat.

Treatment recommendations are individualized, taking into consideration the biology of the cancer, its stage and the overall health of the individual.

Treatment for breast cancer usually includes a combination of surgery, radiation and drug therapy. Surgery and radiation focus on the disease in the breast and lymph nodes, and are referred to as “locoregional” therapies.

Drugs (medical therapies) focus on eliminating breast cancer cells that have traveled through the bloodstream and invaded other organs such as the liver, lungs or bones. Medical therapies are also often used in early-stage breast cancer to destroy microscopic cancer cells hiding in other organs, reducing the risk of advanced-stage breast cancer.

Treatment for breast cancer that has metastasized (spread beyond the breast and lymph nodes as seen on tests such as CAT scans, PET scans or bone scans) generally focuses on drugs that circulate to wherever cancer cells are located. However, localized treatment to specific metastatic lesions (collections of cancer cells) may sometimes be useful.

Surgery

In the past, doctors thought that mastectomy (full removal of the breast) was the best way to improve the chances that the cancer would not return. However, mastectomy does not completely eliminate the chances of the tumor coming back. For many, lumpectomy (removal of the tumor and surrounding tissue but preserving the breast) plus radiation is equally effective. Lumpectomy also has the advantage of offering a better cosmetic result and a shorter recovery time than mastectomy.

In either a mastectomy or a lumpectomy, the surgeon often removes one or more lymph nodes in the underarm near the affected breast to see if they contain cancer cells. In some cases, the surgeon will remove only the sentinel lymph node(s), the first few lymph node(s) into which breast cancer cells may have spread. If the sentinel lymph node is cancer-free, chances are that other lymph nodes are also unaffected and can be left in place, reducing the risk of lymphedema, a painful swelling of the arm that sometimes results from the removal of lymph nodes.

Radiation

Radiation to the entire breast, usually given over 6 weeks, has been the standard of care for those who have been treated with lumpectomy. Recent trials have shown that, in some cases, higher daily doses of radiation given over 3 weeks (with the same total combined dose of radiation) are as effective as the standard approach, with similar potential side effects.

There are other radiation options that can also be considered:

Accelerated partial breast irradiation (APBI) is given only to the area of the breast in which the cancer is present. APBI delivers more radiation in a shorter treatment period.
Brachytherapy uses tiny radioactive pellets or catheters, surgically inserted during a lumpectomy, to deliver a localized dose of radiation.

Some people who have undergone a mastectomy will require post-surgery radiation. Factors that increase the likelihood that radiation after a mastectomy will be required include larger tumor size, the presence of affected lymph nodes and positive margins (cancer cells at the edge of the removed tissue).

Drug Therapy

Drug therapy is an important treatment option for many who have breast cancer. These therapies work by traveling through the bloodstream to destroy cancer cells.

Chemotherapy

Chemotherapy can be an important part of treatment for both early stage and metastatic breast cancer. In particular, triple-negative breast cancer (TNBC) often responds well to chemotherapy.

Based on clinical trials over many years, doctors have learned how to use chemotherapy more effectively, either alone or in combination with other treatments. Doses and schedules of chemotherapy have been refined so that the most benefits are received from treatment with the fewest possible side effects.

Chemotherapy can be used before surgery (preoperative, also called neoadjuvant therapy) to try to shrink the tumor so the surgery can be less extensive, or after surgery (adjuvant) to try to kill any remaining cancer cells. In some cases, the use of preoperative chemotherapy can also provide the doctor with information on how sensitive the cancer cells are to the treatment, which may guide further therapy. It can also be used in cases where the breast cancer has metastasized.

The most common chemotherapy drugs used to treat breast cancer include:

Anthracyclines, such as doxorubicin (Adriamycin), pegylated liposomal doxorubicin (Doxil, Caelyx) and epirubicin (Ellence).
Antimetabolites, such as capecitabine (Xeloda) and gemcitabine (Gemzar).
Antimicrotubule agents, such as ixabepilone (Ixempra), eribulin (Halaven) and Vinorelbine (Navelbine).
Platinum agents, such as platitinol (Cisplatin) and carboplatin (Paraplatin).
Taxanes, such as paclitaxel (Taxol), docetaxel (Taxotere) and albumin-bound paclitaxel (Abraxane).

A note about chemotherapy in the treatment of metastatic breast cancer

In addition to treating triple-negative metastatic breast cancer, chemotherapy can be given for hormone-positive metastatic breast cancer that is no longer responding to hormone therapy and for HER2-positive metastatic breast cancer (in combination with anti-HER2 treatments).

Hormone (Endocrine) Therapy

Doctors will often recommend hormone therapy as a treatment for early stage and metastatic ER-positive and/or PR-positive breast cancer. Hormone treatments work in different ways. Some are designed to prevent estrogen from attaching to receptors in breast cancer cells, while others are designed to reduce the level of hormones that circulate in the body. By blocking the effects of estrogen or lowering levels of estrogen, these treatments deprive tumor cells of the stimulation that fuels their growth.

The most common hormone therapies used to treat ER-positive or PR-positive breast cancer include:

Tamoxifen (Soltamox, Nolvadex) is an estrogen-blocking treatment given to both pre- and postmenopausal individuals with breast cancer. Studies have shown that taking tamoxifen for five years following surgery reduces the chance of the cancer recurring by fifty percent. For anyone with cancer in one breast, tamoxifen also lowers the risk of a new tumor developing in the unaffected breast.
Some studies have shown that taking tamoxifen for ten years can be even more beneficial for those at higher risk of recurrence. For those with metastatic breast cancer, tamoxifen can shrink the tumor, prolong progression-free survival (the time in which the tumor does not grow) and improve overall survival.
Tamoxifen has also been approved as chemoprevention, reducing the chance of ER-positive breast cancer developing in healthy pre- or postmenopausal individuals who are at high risk for breast cancer, with the preventive benefits of the drug extending for many years beyond when the drug is taken.
Healthy individuals who are at high risk for developing breast cancer should talk with their doctors about whether taking tamoxifen for breast cancer prevention is a good option for them. The doctor will consider multiple factors such as age, family history, biopsy results and reproductive history.
Aromatase inhibitors (AIs), another type of hormone therapy, are given to postmenopausal individuals with early-stage ER-positive breast cancer to help prevent cancer from returning after surgery. In some situations, AIs can also be used for the treatment of premenopausal individuals, along with medications to artificially induce menopause (see next section: “Ovarian Suppression”). AIs block the action of an enzyme called aromatase, cutting off the supply of estrogen (estrogen can stimulate tumor growth). AIs are also commonly used to treat metastatic breast cancer, sometimes in combination with targeted therapies. They have also shown effectiveness in breast cancer prevention.
The AIs primarily used to treat breast cancer are anastrozole (Arimidex), letrozole (Femara) and exemestane (Aromasin). Taking AIs for five years (either alone or after five years of tamoxifen) can help reduce recurrence in postmenopausal individuals with ER-positive breast cancer.
Fulvestrant (Faslodex) is another estrogen-blocking drug. It works by attaching to estrogen receptors, changing their shape and preventing the receptors from working properly, which slows the growth of breast cancer cells. Fulvestrant is given as a monthly injection and is approved for postmenopausal individuals with metastatic breast cancer.

Ovarian Suppression (Combined with Tamoxifen or Aromatase Inhibitors)

The estrogen produced by the ovaries can fuel tumor growth. Ovarian suppression uses drug therapy or surgery to stop the ovaries from producing estrogen. Some younger, premenopausal individuals with hormone receptor-positive breast cancer may benefit from treatment with ovarian suppression drugs, combined with tamoxifen or an aromatase inhibitor. Ovarian suppression drugs include leuprolide (Lupron) and goserelin (Zoladex).

Targeted Therapy

Targeted therapy focuses on specific molecules and cell mechanisms thought to be important for cancer cell survival and growth, taking advantage of what researchers have learned in recent years about how cancer cells grow.

A number of targeted therapies have been developed for the treatment of breast cancer:

Trastuzumab (Herceptin) is the standard treatment for HER2-positive breast cancer. Typically taken for one year in the treatment of early-stage breast cancer, trastuzumab can also be given over longer periods to treat cases of metastatic disease.
Lapatinib (Tykerb) is able to block HER2 signals from within cancer cells, and has shown to be effective in treating cases where HER2-positive breast cancer has returned, spread or continued growing after treatment with trastuzumab and chemotherapy.
Pertuzumab (Perjeta) was approved by the U.S. Food and Drug Administration (FDA) in 2012 for metastatic HER2-positive breast cancer and in 2013 as a neoadjuvant treatment option for HER2-positive breast cancer when used in combination with trastuzumab and chemotherapy (docetaxel or paclitaxel). In December 2017, pertuzumab’s approval was extended for use as an adjuvant treatment for HER2-positive breast cancer, also in combination with trastuzumab and chemotherapy.
Ado-trastuzumab emtansine (Kadcyla), an antibody drug conjugate also known as T-DM1, is a combination of trastuzumab and a chemotherapy drug used to treat HER2-positive metastatic breast cancer. Additionally, in May 2019 the FDA approved T-DM1 for the treatment of those with early-stage HER2-positive breast cancer whose tumors do not completely respond to neoadjuvant treatments.
Trastuzumab deruxtecan (Enhertu), an antibody drug conjugate, was approved in December 2019 for the treatment of unresectable (inoperable) or metastatic HER2-positive breast cancer following two or more anti-HER2-based regimens. In May 2022, the FDA updated the approval of trastuzumab deruxtecan for the treatment of metastatic HER2-positive breast cancer following anti-HER2 therapy. In August 2022, the approval of trastuzumab deruxtecan was expanded for the treatment of unresectable or metastatic HER2-low breast cancer previously treated with chemotherapy.
Neratinib (Nerlynx). In July 2017, the FDA approved the tyrosine kinase inhibitor neratinib as an adjuvant therapy to further reduce recurrence in those with early-stage HER2-positive breast cancer who have finished at least one year of post-surgery therapy with trastuzumab.
Tucatinib (Tukysa). In April 2020, the FDA approved tucatinib, in combination with trastuzumab and the chemotherapy capecitabine, for the treatment of HER2-positive metastatic breast cancer.
Margetuximab-cmkb (Margenza). Margetuximab-cmkb, in combination with chemotherapy, is used for the treatment of HER2-positive metastatic breast cancer that was previously treated with at least two anti-HER2 regimens. Margetuximab-cmkb was approved by the FDA in December 2020.
Sacituzumab govitecan-hziy (Trodelvy), an antibody drug conjugate, was approved by the FDA in April 2021 for the treatment of unresectable locally advanced or metastatic triple-negative breast cancer that was previously treated with two or more therapy regimens, at least one of them for metastatic disease.
Capivasertib (Truqap), approved by the FDA in November 2023, is used to treat HR-positive, HER2-negative locally advanced or metastatic breast cancers that test positive for certain gene mutations. Capivasertib targets the AKT protein, which helps regulate cell growth and division.

Other therapies that have been developed for use based on individual circumstances include:

mTOR inhibitors. Everolimus (Afinitor) is a targeted therapy that works inside cancer cells to restore their sensitivity to anti-estrogen therapies such as AIs. In treating breast cancer, everolimus seems to help hormone therapy work more effectively, but it may cause increased side effects. Taken once daily with the AI exemestane, everolimus treats advanced hormone receptor-positive, HER2-negative breast cancer in postmenopausal cases where the cancer has continued to grow after treatment with another AI.

CDK4/6 inhibitors. These therapies are designed to interrupt enzymes that promote the growth of cancer cells. The CDK4/6 inhibitors used in treating ER-positive, HER2-negative metastatic breast cancer are abemaciclib (Verzenio), palbociclib (Ibrance) and ribociclib (Kisqali). Each of these medications can be given in combination with hormone therapy, such as the AI letrozole or the hormone therapy fulvestrant. Abemaciclib can also be used as a monotherapy (a medication given alone). In March 2023, the FDA approved abemaciclib with endocrine therapy for the adjuvant treatment of HR-positive, HER2-negative, node-positive early breast cancer at high risk of recurrence.

PARP inhibitors. PARP is a type of enzyme that helps repair DNA. In cancer treatment, PARP inhibitors are used to prevent cancer cells from repairing their damaged DNA. This prevention can cause the cancer cells to die, especially those with defective DNA repair pathways, such as BRCA1/2-associated breast cancers. Talazoparib (Talzenna) is approved for the treatment of BRCA-positive, HER2-negative metastatic breast cancer. Olaparib (Lynparza) is approved for the treatment of BRCA-positive, HER2-negative metastatic breast cancer that was previously treated with chemotherapy, and in the adjuvant (after surgery) setting for patients with high-risk triple negative or HR-positive breast cancer.

Immunotherapy. In November 2020, the FDA granted accelerated approval to pembrolizumab (Keytruda) in combination with chemotherapy for the treatment of locally recurrent unresectable (inoperable) or metastatic triple-negative breast cancer whose tumors express high levels of the protein PD-L1. In July 2021, the FDA approved pembrolizumab for the treatment of high-risk, early-stage triple-negative breast cancer in combination with chemotherapy as a preoperative treatment and then continued as a monotherapy after surgery.

PIK3CA inhibitor. In May 2019, the FDA approved alpelisib (Piqray), in combination with the endocrine therapy fulvestrant, to treat HR-positive, HER2-negative, PIK3CA-mutated metastatic breast cancer following treatment with an endocrine-based therapy.

Antibody-drug conjugate. In April 2020, the FDA approved sacituzumab govitecan-hziy (Trodelvy) for metastatic triple-negative breast cancer that had been treated by at least two prior therapies. In February 2023, the approval of sacituzumab govitecan-hziy was expanded to include the treatment of locally advanced or metastatic HR-positive, HER2-negative/HER2-low breast cancer that was previously treated with hormone-based therapy and at least two additional systemic therapies in the metastatic setting.

Selective Estrogen Receptor Degrader (SERD). Elacestrant (Orserdu) is approved for the treatment of ER-positive, HER2-negative/HER2-low, ESR1-mutated advanced or metastatic breast cancer following endocrine therapy. SERDs, also known as estrogen receptor antagonists (ERAs), stop estrogen from helping hormone receptor -positive breast cancer cells to grow.

Diagnostic Tests Promising New Treatment Approaches: A Report from the 2023 San Antonio Breast Cancer Symposium

This section presents highlights from the 2023 San Antonio Breast Cancer Symposium, which took place December 5-9 in San Antonio, Texas. The information includes new findings on a number of currently used treatments, as well as promising new treatments that researchers continue to study in clinical trials.

Some of these new treatments are in the earliest phases of research and may not be available to the general public outside of a clinical trial. The information is intended for discussion with your doctor. They can let you know if these research findings affect your treatment plan and whether a clinical trial might be right for you.

Pembrolizumab evaluated beyond triple-negativevbreast cancer

Data from the KEYNOTE-756 trial showed an increase in pathological complete response (a lack of all signs of cancer) when neoadjuvant pembrolizumab was used in the treatment of ER-positive, HER2-negative breast cancer.