> Triple Negative Breast Cancer – what do we know and where are we headed?
Although breast cancer is often referred to as one disease, there are actually many different types of breast cancer. The differences can help guide treatment and provide information on prognosis. Certain characteristics make some breast cancers more aggressive than others, leading to a poorer prognosis. One such breast cancer is triple negative breast cancer. Although we understand some aspects of these breast cancers, we still have much to learn.
What is triple negative breast cancer?
All breast cancers are tested for hormone (estrogen and progesterone) receptors and HER2/neu receptors. If the test is “positive”, the cancer cells have many receptors. If the test is “negative”, the cancer cells have few or no receptors. The status of these receptors helps guide treatment. Triple negative breast cancers are:
About 14 to 20 percent of all breast cancers are triple negative.1-7
Who gets triple negative breast cancer?
Triple negative breast cancers tend to occur more often in:1,4-6,8-11
Race/ethnicity and triple negative breast cancer
Triple negative breast cancers appear to be more common among African American women (especially those who are premenopausal) compared to white women.1,5,10,12-16 Although the reasons for this are not clear, some studies suggest lifestyle factors might play a role. Some findings show African American women tend to have lower rates of breastfeeding, to give birth to more children and to carry excess weight in the abdomen area compared to other women, all of which may increase the chances of having triple negative breast cancer.7,17-20
BRCA1 and BRCA2 gene mutations and triple negative breast cancer
Inherited mutations in the BRCA1 and BRCA2 genes (BReast CAncer genes 1 and 2) are linked to breast cancer risk. People who carry these mutations have an increased risk of breast cancer (learn more).21
Most BRCA1-related breast cancers and some BRCA2-related breast cancers are triple negative.8-9 The relationship between triple negative cancers and BRCA1 and BRCA2 genetic mutations is under study and may help identify new treatments.
Risk factors for triple negative breast cancer
Most risk factors affect the risk of triple negative breast cancer in the same way they affect the risk of other breast cancers. For example, breastfeeding lowers the risk of breast cancer, including the risk of triple negative breast cancer.16,22-23
Some factors, however, appear to impact the risk of triple negative breast cancers differently than they impact the risk of other breast cancers.
In general, women who have given birth to more than one child have a lower risk of breast cancer than women who have never given birth. However, women may not get this protective benefit of childbearing for triple negative breast cancers.7,16,19 On the other hand, although having a child a later age tends to increase the risk of breast cancer, it does not appear to increase the risk of triple negative cancers.7 These topics are under active study.
Being overweight tends to lower the risk of breast cancer before menopause and increase the risk of breast cancer after menopause.24-26 However, being overweight may increase the risk of both premenopausal and postmenopausal triple negative breast cancer.7
Triple negative breast cancers are treated with a combination of surgery, radiation therapy and chemotherapy. Because triple negative breast cancers are ER-, PR- and HER2-, they cannot be treated with hormone therapy (only used to treat estrogen receptor-positive and progesterone receptor-positive cancers) or trastuzumab (Herceptin) (only used to treat HER2/neu-positive cancers). Fortunately, chemotherapy can be effective in treating these breast cancers.
Sometimes chemotherapy is given before surgery (called neoadjuvant chemotherapy), rather than after surgery. Neoadjuvant chemotherapy can increase a woman’s breast surgery options. It can shrink a tumor enough that a lumpectomy becomes an option to a mastectomy. The response to neoadjuvant chemotherapy may also give information on prognosis. If a triple negative tumor responds well to neoadjuvant chemotherapy, the chances of survival are higher than when there is a poor response to this early treatment.27-28
Breast cancer recurrence and survival
Triple negative breast cancers appear more likely to recur than other breast cancers.29 Recurrence for these cancers often involves metastasis (when cancer spreads to other organs), especially to the brain or lungs. Triple negative breast cancers tend to recur within a few years and when they recur, prognosis is usually poor.29-30
However, because triple negative breast cancers tend to recur early, if a woman survives five years without a recurrence, her chances of survival are high.29 This is good news for five-year survivors and makes this milestone especially important for women diagnosed with triple negative breast cancer.
Although many triple negative breast cancers can be successfully treated, overall they have a poorer prognosis than other breast cancers. The main reason for this is the lack of a targeted treatment. However, new treatments are under study.
Emerging areas in treating triple negative breast cancer
Clinical trials of treatments for triple negative breast cancer are underway. Promising new treatments (in combination with chemotherapy) include PARP inhibitors, bevacizumab and other targeted therapies.
Poly (ADP-ribose) polymerase (PARP) is an enzyme involved in DNA repair. Some chemotherapy drugs damage DNA. Adding a PARP inhibitor may lower the chances the cancer cells become resistant to the chemotherapy. When cancer cells become resistant to chemotherapy, the chemotherapy is no longer able to fight the cancer cells. So, by lowering the chances of resistance, the PARP inhibitor may increase the effectiveness of the chemotherapy.
The PARP inhibitor olaparib may benefit women with triple negative breast cancers who carry a BRCA1 or BRCA2 gene mutation.31 In one early study, iniparib (not a pure PARP inhibitor) seemed to benefit triple negative breast cancers, but this has not been confirmed in larger studies.32
Although these findings show promise for PARP inhibitors in the treatment of triple negative breast cancers, the studies included only a small number of women followed over a short time. And, studies suggest the potential benefit of PARP inhibitors may be limited to BRCA1- and BRCA2-related breast cancers. Larger, longer-term studies are underway to confirm these findings.
The genes linked to triple negative breast cancer are not well understood at this time. Thus, targeted therapies do not yet exist to treat these cancers. Potential targets for future therapies include the epidermal growth factor receptor (EGFR), aB-crystallin and cyclin E.33
Although the drug bevacizumab (Avastin) is no longer FDA-approved for the treatment of metastatic breast cancer, it is still under active study for the treatment of triple negative breast cancers.
Learn about Susan G. Komen for the Cure’s® work with the Triple Negative Breast Cancer Foundation (TNBC) and research we are funding to study triple negative breast cancer.
Joining a clinical trial
If you are newly diagnosed with breast cancer (triple negative or other type), we encourage you to consider joining a clinical trial. Talk to your health care provider or visit our clinical trial section for more information.
In collaboration with BreastCancerTrials.org we offer a custom matching service to help you find a clinical trial that fits your health needs. Learn more about this program.
According to Dr. Eric Winer, our chief scientific advisor, and director of the Breast Oncology Center and the Thompson Senior Investigator in Breast Cancer Research at Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, “At this time, triple negative breast cancer remains one of the most challenging subtypes of breast cancer. Treatment options are more limited than for other women with breast cancer, but triple negative disease is an area of very active research. Importantly, many women do well with our standard therapies and we anticipate great progress over the next decade.”
Learn more about:
- Carey LA, Perou CM, Livasy CA, et al. Race, breast cancer subtypes, and survival in the Carolina Breast cancer Study. JAMA. 295(21):2492-2502, 2006.
- Fan C, Oh DS, Wessels L, et al. Concordance among gen-expression-based predictors for breast cancer. N Engl J Med. 355(6):560-9, 2006.
- Hannemann J, Kristel P, van Tinteren H, et al. Molecular subtypes of breast cancer and amplification of topoisomerase II alpha: predictive role in dose intensive adjuvant chemotherapy. Br J Cancer. 95(10):1334-41, 2006.
- Yang XR, Sherman ME, Rimm DL, et al. Differences in risk factors for breast cancer molecular subtypes in a population-based study. Cancer Epidemiol Biomarkers Prev. 16(3):439-43, 2007.
- Stead LA, Lash TL, Sobieraj JE, et al. Triple-negative breast cancers are increased in black women regardless of age or body mass index. Breast Cancer Res. 11(2):R18, 2009.
- Lund MJ, Butler EN, Hair BY, et al. Age/race differences in HER2 testing and in incidence rates for breast cancer triple subtypes: a population-based study and first report. Cancer. 116(11):2549-59, 2010.
- Yang XR, Chang-Claude J, Goode EL, et al. Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies. J Natl Cancer Inst. 103(3):250-63, 2011.
- Turner NC, Reis-Filho JS. Basal-like breast cancer and the BRCA1 phenotype. Oncogene. 25(43):5846-53, 2006.
- Atchley DP, Albarracin CT, Lopez A, et al. Clinical and pathologic characteristics of patients with BRCA-positive and BRCA-negative breast cancer. J Clin Oncol. 26(26):4282-8, 2008.
- Amirikia KC, Mills P, Bush J, Newman LA. Higher population-based incidence rates of triple-negative breast cancer among young African-American women: Implications for breast cancer screening recommendations. Cancer. 117(12):2747-53, 2011.
- Dawood S, Hu R, Homes MD, et al. Defining breast cancer prognosis based on molecular phenotypes: results from a large cohort study. Breast Cancer Res Treat. 126(1):185-92, 2011.
- Ihemelandu CU, Leffall LD Jr, Dewitty RL, et al. Molecular breast cancer subtypes in premenopausal African-American women, tumor biologic factors and clinical outcome. Ann Surg Oncol. 14(10):2994-3003, 2007.
- Bowen RL, Duffy SW, Ryan DA, Hart IR, Jones JL. Early onset of breast cancer in a group of British black women. Br J Cancer. 98(2):277-81, 2008.
- Lund MJ, Trivers KF, Porter PL, et al. Race and triple negative threats to breast cancer survival: a population-based study in Atlanta, GA. Breast Cancer Res Treat. 113(2):357-70, 2009.
- Shinde SS, Forman MR, Kuerer HM, et al. Higher parity and shorter breastfeeding duration: association with triple-negative phenotype of breast cancer. Cancer. 116(21):4933-43, 2010.
- Stark A, Kleer CG, Martin I, et al. African ancestry and higher prevalence of triple-negative breast cancer: findings from an international study. Cancer. 116(21):4926-32, 2010.
- Gaudet MM, Press MF, Haile RW, et al. Risk factors by molecular subtypes of breast cancer across a population-based study of women 56 years or younger. Breast Cancer Res Treat. 130(2):587-97, 2011.
- Palmer JR, Boggs DA, Wise LA, Ambrosone CB, Adams-Campbell LL, Rosenberg L. Parity and lactation in relation to estrogen receptor negative breast cancer in African American women. Cancer Epidemiol Biomarkers Prev. 20(9):1883-91, 2011.
- Phipps AI, Chlebowski RT, Prentice R, et al. Reproductive history and oral contraceptive use in relation to risk of triple-negative breast cancer. J Natl Cancer Inst. 103(6):470-7, 2011.
- Tamimi RM, Colditz GA, Hazra A, et al. Traditional breast cancer risk factors in relation to molecular subtypes of breast cancer. Breast Cancer Res Treat. 131(1):159-67, 2012.
- National Cancer Institute. Genetics of breast and ovarian cancer (PDQ). http://www.cancer.gov/cancertopics/pdq/genetics/breast-and-ovarian/HealthProfessional/page2, 2011.
- Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and breast feeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50,302 women with breast cancer and 96,973 women without the disease. Lancet 20:187-95, 2002.
- Phipps AI, Malone KE, Porter PL, Daling JR, Li CI. Reproductive and hormonal risk factors for postmenopausal luminal, HER-2-overexpressing, and triple-negative breast cancer. Cancer. 113(7):1521-6, 2008.
- Huang Z, Hankinson SE, Colditz GA, et al. Dual effects of weight and weight gain on breast cancer risk. JAMA. 278: 1407-11, 1997.
- van den Brandt PA, Spiegelman D, Yaun SS, et al. Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol. 152:514-27, 2000.
- Reeves GK, Pirie K, Beral V, Green J, Spencer E, Bull D. Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study. BMJ. 335(7630):1134, 2007.
- Carey LA, Dees EC, Sawyer L, et al. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 13(8):2329-34, 2007.
- Liedtke C, Mazouni C, Hess KR, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 26(8):1275-81, 2008.
- Dent R, Hanna WM, Trudeau M, Rawlinson E, Sun P, Narod SA. Pattern of metastatic spread in triple-negative breast cancer. Breast Cancer Res Treat. 115(2):423-8, 2009.
- Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med. 363(20):1938-48, 2010.
- Fong PC, Boss DS, Yap TA, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 361(2):123-34, 2009.
- O'Shaughnessy J, Osborne C, Pippen JE, et al. Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med. 364(3):205-14, 2011.
- Yehiely F, Moyano JV, Evans JR, Nielsen TO, Cryns VL. Deconstructing the molecular portrait of basal-like breast cancer. Trends Mol Med. 12(11):537-44, 2006.
Posted February 14, 2012