October is Breast Cancer Awareness Month. But for the 291,840 women who will be diagnosed with breast cancer in the United States this year, and the 2.8 million women living with a history of breast cancer, that awareness lasts all year. And women aren’t the only ones affected by breast cancer: about 2,350 men are estimated to be diagnosed with breast cancer in 2015. With 1 in 8 women diagnosed with breast cancer in her lifetime, this disease hits close to home for many people and families. Despite early diagnosis and improved treatments, more than 39,000 patients die of breast cancer every year in this country. Breast cancer is the second leading cause of death among women.
Gender and age. The biggest risk factors for breast cancer are being a woman and older age. More than 65% of invasive breast cancers (spread within the breasts) are found in women aged 55 and older. Genetics. A family history of breast cancer is another important risk. The risk doubles for a woman with a first-degree female relative (sister, mother, or daughter) who was diagnosed with breast cancer. Mutations (changes) in the BRCA gene run in families and can be inherited by family members; these mutations are responsible for 5% to 10% of all female breast cancers. For those with BRCA1 or BRCA2 gene mutation, the risk for breast cancer is 45% to 65%. Jewish women of European descent are at a high risk for this specific type of cancer. Reproductive factors that affect risk include longer-than-average menstrual history, recent use of oral contraceptives or Depo-Provera, never having children, or having your first child after age 30. Women who breastfeed for at least 1 year tend to have a lower risk.
Race and ethnicity also play a role. White women are slightly more likely to have breast cancer than African-American, Hispanic, or Asian women, but African-American women are more likely to be diagnosed at a younger age, and with more aggressive and more advanced disease. All women of Ashkenazi Jewish ancestry should be tested for the BRCA mutation, because they have a 10 times greater risk than other women to inherit this gene. Lifestyle. Some lifestyle factors also increase the risk for breast cancer, including obesity, lack of physical activity, excessive alcohol consumption, and use of hormone therapy. Studies continue to uncover lifestyle and environmental risk factors, such as low levels of vitamin D and exposure to chemicals used in cosmetics, sunscreen, food, plastic, and lawns and gardens. Personal history. Women who have had breast cancer are 3 to 4 times more likely to have new (not recurrent) cancer. In addition, those who receive high-dose radiation to the chest for the treatment of cancer at a young age are also at an increased risk for a new cancer later on.
Breast cancer often has no obvious symptoms, and those that do exist vary widely. Breast pain is rarely a symptom of cancer. The most common symptom is a painless lump or mass in the breast. Less common symptoms include changes to the breast, such as:
- Swelling or distortion
- Skin irritation or redness
- Nipple abnormalities, such as ulceration or retraction
- Nipple discharge
SCREENING AND DIAGNOSIS
Screening for breast cancer includes an annual physical breast exam and mammography, recommended for all women starting at age 40. For women at higher risk, doctors may recommend a breast MRI beginning at age 30. Women with a family history of breast cancer should discuss the need for genetic testing with their healthcare provider. According to the American Cancer Society, 10% of all women have abnormal mammograms, but most (95%) of those women don’t have cancer. A biopsy is needed to confirm the diagnosis; it involves removal of tissue from a suspicious area of the breast. If breast cancer is diagnosed, additional cells (usually underarm lymph nodes) are removed to determine whether the cancer has spread beyond the breast. New genetic tests are helping to identify patients with specific genetic characteristics that can benefit from different types of therapy: Oncotype DX is a genetic test that identifies the stage of cancer and the risk for recurrence and helps to determine the course of therapy. A new study just published indicates that patients with early breast cancer who are HER2-negative and have a low score on the Oncotype DX test may use hormone therapy alone and skip chemotherapy, without hurting their chance for recovery. MammaPrint is another genomic test that identifies the risk that the cancer will return in patients with certain genetic makeup and early-stage breast cancer.
STAGES OF BREAST CANCER
Based on the results of the biopsy and the lymph node evaluation, the stage (size) of the cancer is determined. Stage 0 (called carcinoma in situ) means that the cancer cells are placed within the milk ducts and have not invaded breast tissue. Carcinoma in situ is the most curable form of breast cancer; however, if left untreated, it can spread and become invasive breast cancer. Stage I and II are considered early breast cancer. In stage I, the tumor is less than 2 centimeters; in stage II, it is larger than 2 centimeters but has not spread beyond the breast to the lymph nodes or other organs. Stage III and IV breast cancer indicate that cancer cells have spread to the lymph nodes or other organs (that is, metastatic disease). Only 5% of initial diagnoses are metastatic. Most (61%) breast cancers are diagnosed at an earlier stage, when the cancer is localized within the breast and is easier to treat and even cure.
Breast cancer treatment is tailored to the specific type and stage of the cancer, the overall health and age of the patient, and the patient’s personal preferences. Treatment usually involves breast-conserving surgery (the tumor and surrounding tissue are removed) or mastectomy (removal of 1 or 2 breasts). Treatment also may involve radiation therapy, chemotherapy, hormone therapy, and/or targeted therapy (drugs targeted directly at the tumor). Early-stage breast cancer can often be successfully treated today with surgery, chemotherapy, and radiation, although the approach to therapy at an early stage is changing rapidly. As noted above, a newly published study indicates that certain patients with early-stage disease can skip chemotherapy without hurting their chance for a successful treatment.
The treatment options for metastatic disease include hormone therapy, radiation therapy, and chemotherapy. The goal of treatment is to prolong survival, while focusing on the patient’s quality of life, because there is no cure for the disease at this stage. In addition, women with advanced breast cancer often receive drugs that can strengthen bones and reduce bone fractures, such as Zometa (zoledronic acid), Xgeva (denosumab), and Prolia (denosumab). In recent years, cancer research has focused on identifying specific genes, molecules, and proteins that cause cancer and its growth and spread, with the goal of developing therapies that can stop the spread of cancer cells. One of the first examples is Herceptin (trastuzumab), which changed the treatment of breast cancer when it was approved by the FDA in 1998. Herceptin was developed after studies showed that the HER2 gene plays a critical role in a particularly aggressive type of breast cancer that does not respond well to regular chemotherapy. Herceptin significantly improved survival. Because the HER2 gene is involved in approximately only 25% of all breast cancers, drugs that target other genes and molecules involved in breast cancer were clearly needed.
This led to the development of other targeted drugs in the past decade for patients with metastatic disease, with and without the HER2 gene:
- Tykerb (lapatinib) was approved in March 2007 for HER2-positive disease. In January 2010, Tykerb was approved in combination with Femara (letrozole) for postmenopausal women with HER2-positive disease
- Halaven (eribulin) was approved in November 2010 for metastatic disease
- Perjeta (pertuzumab) was approved in June 2012 for HER2-positive metastatic disease. In September 2013, Perjeta was approved, in combination with Herceptin and Taxotere (docetaxel), for neoadjuvant (before surgery), early-stage disease
- Afinitor (everolimus), in combination with Aromasin (exemestane), was approved in July 2012 for HER2-negative disease
- Kadcyla (ado-trastuzumab emtansine) was approved in February 2013 for HER2-positive disease
- Ibrance (palbociclib), in combination with letrozole, was approved in February 2015 for postmenopausal women with HER2-negative disease
ON THE HORIZON
A new drug class targeting cancers caused by BRCA gene mutations are called PARP inhibitors, which have shown promise in treating breast cancer that had spread and does not respond to other therapies. A retinoid, fenretinide is being studied for reducing the risk for breast cancer; other drugs being studied include aromatase inhibitors, and antiangiogenesis drugs. As long as breast cancer affects hundreds of thousands of women and causes the deaths of tens of thousands of women annually, the search for more effective breast cancer therapy will continue.