Triple-Negative Breast Cancer

Picture of breast cancer symptoms

Breast cancer is a malignancy (a collection of cancer cells) arising from the cells of the breast. Triple-negative breast cancer means the cancer does not express three common markers often found on breast cancer cells: the estrogen receptor (ER), progesterone receptor (PR), and a protein involved in cell growth known as HER2. Triple-negative breast cancer makes up about 10%-20% of all breast cancers.

Although there are known risk factors for the development of any kind of breast cancer, doctors do not understand the exact cause of breast cancer.

• Normal cells become cancer cells due to changes or mutations in the DNA.
• While people inherit some DNA changes, others acquire these DNA changes during a person's life.

The following are causes and risk factors for any type of breast cancer, including triple-negative breast cancer:

• Increasing age
• Family history of breast cancer
• Personal history of breast cancer
• Certain kinds of benign breast disease (atypical hyperplasia)
• Young age at menstruation or late menopause
• Dense breast tissue
• Radiation exposure
• Having never given birth or giving birth for the first time after age 30
• Overweight and obesity
• Postmenopausal hormone therapy use
• Alcohol consumption
• Genetic risk factors (BRCA-1 and BRCA-2 mutations)

Unlike most breast cancer, which is more common in Caucasian women, triple-negative breast cancer is more common in African-American and Hispanic women. It is also more likely to occur in younger women. About 70% of cancers that occur in women with a BRCA-1 mutation are triple-negative.

Triple-negative breast cancers may not cause any symptoms at all. When they do cause signs and symptoms, a painless hard mass in the breast is the most common sign.

Other symptoms and signs are less common and can include

• changes in the skin of the breast,
• lumps or masses felt in the armpit, and
• changes in the nipple, including inversion of the nipple and nipple discharge.

The diagnosis of triple-negative breast cancer requires a sampling of tissue from the breast, known as a breast biopsy.

• Medical professionals may perform the biopsy using imaging techniques, such as mammography or others, for guidance.
• If the biopsy shows cancer, they may perform other tests on the biopsy sample (or on a sample of tumor removed surgically) to determine the precise type of cancer.
• In particular, they commonly perform tests for expression of the estrogen receptor (ER), progesterone receptor (PR), and HER2 protein as a first step. If these tests are all negative, they classify cancer as triple-negative breast cancer.

Staging is the process of determining the extent of cancer and its spread in the body. Together with the type of cancer, staging helps determine the appropriate therapy and predict the chances for survival.

To determine if cancer has spread, medical professionals may use several different imaging techniques, including X-ray, CT scans, bone scans, and PET scans. Staging depends upon the size of a tumor and the extent to which it spread to lymph nodes or distant sites and organs in the body. Examination of lymph nodes removed at surgery and the results of ER, PR, and HER2 tests performed on the tumor tissue also help determine the stage of a tumor.

• The American Cancer Society defines 4 stages of breast cancer.
• Stage I is the lowest stage, while stage IV is the highest stage and refers to tumors that have metastasized, or spread to areas distant from the breast.

Most doctors specifically adjust breast cancer treatments to the type of cancer and the staging group.

Surgery

Many women with breast cancer will require surgery. Broadly, the surgical therapies for breast cancer consist of breast-conserving surgery (lumpectomy, or partial removal of the breast) and mastectomy (complete removal of the breast).

Radiation therapy

Radiation therapy destroys cancer cells with high-energy rays. Doctors commonly administer radiation therapy to patients after breast cancer surgery, most commonly after lumpectomy.

Chemotherapy

Doctors typically recommend chemotherapy for the treatment of triple-negative breast cancers larger than 0.5 cm. Unlike cancers that express hormone receptors (ER and PR) or HER2, anti-hormonal therapy or HER2-targeted therapy is not effective. Medical professionals administer chemotherapy treatments by intravenous injection or by mouth.

Types of chemotherapy include the following:

• Adjuvant chemotherapy is chemotherapy given after surgery to remove cancer or after mastectomy.
• Neoadjuvant chemotherapy is chemotherapy given before surgery. Although there seems to be no advantage to long-term survival whether a patient receives the therapy before or after surgery, it may be advantageous in some cases to give the chemotherapy before surgery to see if cancer responds and to shrink cancer before surgical removal.
• Chemotherapy for advanced cancer: If cancer has metastasized to distant sites in the body, chemotherapy can be used for treatment. The immunotherapy medicine atezolizumab (Tecentriq) in combination with the chemotherapy medicine Abraxane is also used for some cases of metastatic triple-negative breast cancer.

Other therapies for triple-negative breast cancer

In March 2019, the U.S. Food and Drug Administration (FDA) approved a new combination therapy for metastatic triple-negative breast cancer consisting of a combination of an immunotherapy drug and chemotherapy.

Survival rates are a way to discuss the prognosis and outlook of a cancer diagnosis. The number most frequently mentioned is 5-year survival. Many patients live much longer, and some die earlier from causes other than breast cancer. With constant change and improvement in therapies, these numbers also change. Current 5-year survival statistics are based on patients who were diagnosed at least 5 years ago and may have received different therapies than are available today.

Below are the statistics from the National Cancer Institute's SEER database for the survival of all patients with breast cancer, by tumor stage:

Patients with triple-negative breast cancer tend to have a worse prognosis, although the American Cancer Society does not report specific survival statistics in their patient materials for people with triple-negative breast cancer. One study in 2007 showed that 77% of women with triple-negative breast cancer survived for at least 5 years, compared with 93% of women with other types of breast cancer. A 2009 study of a smaller number of patients did not show a difference in survival between the types of breast cancer. Recent research focused on looking at the group of triple-negative breast cancers to try to identify subtypes of this group that may have a more favorable prognosis. While survival rates for many people with the disease may be somewhat lower, with effective treatments, the majority of people with triple-negative breast cancer will survive without recurrence of the disease.

What is the recurrence rate for triple negative breast cancer?

• The chances that a triple-negative breast cancer will recur, or come back after treatment, are greater than with other breast cancers.
• This risk of recurrence is greatest at about 3 years after diagnosis.
• Recurrences in the early years are more likely to occur in the lungs or brain and less commonly in the bones than other types of breast cancers.
• However, the risk of late recurrence after 5 years is more common with other types of breast cancer and is less common for people with triple-negative cancer.

There is no guaranteed way to prevent breast cancer, but modifying your lifestyle risk factors (exercising, maintaining a healthy body weight, etc.) can help decrease the risk. Following the American Cancer Society's guidelines for screening and early detection can help with identifying cancers at an early stage when treatment is most effective.

Women with a strong family history of breast cancer should undergo genetic testing. In some cases, the use of medications or surgery may be considered for the prevention of breast cancer in high-risk women, after consultation with a health care professional and a meeting with a genetic counselor.