A multitude of medical studies have shown that a woman?s risk of developing breast cancer is directly related to her exposure to endogenous estrogen and progesterone, hormones that are produced by her ovaries. These ovarian hormones stimulate cell growth. Reproductive factors that increase the duration and/or levels of exposure to these hormones, include early onset of menstruation, late onset of menopause, later age at first pregnancy, and never having given birth have been associated with an increase in breast cancer risk.
Pregnancy and breastfeeding reduce a woman?s lifetime number of menstrual cycles, and, as a result, her cumulative exposure to endogenous hormones [1]. Furthermore, pregnancy and breastfeeding have direct effects on breast cells, causing them to differentiate, or mature, so they can produce milk. Some researchers hypothesize that these differentiated cells are more resistant to being transformed into cancer cells than cells that have not undergone such differentiation. [2][3]
…Observations made in the ELLA study need to be replicated in populations with similar reproductive profiles to determine if the results are due to common biologic factors or specific genetic or environmental factors of the women in the this study…
Until recently, breast cancer was considered relatively rare in Mexico. However, breast cancer is now one the most commonly diagnosed cancer among women in the more industrialized states as well as the northern regions of the country. Recent publication comparing white women in Arizona with Hispanic women shows that overall, Hispanic women are diagnosed with tumors that have a more aggressive pattern and less favorable prognosis.
EllA Study
Now a new study, led by researchers from the University of California, San Diego School of Medicine, published online in Cancer Epidemiology, Biomarkers & Prevention, indicates that women of Mexican descent may not benefit from these protective factors.[4] The published results suggest that women from Mexican descent with more children and those who breastfeed are more likely to be diagnosed with an aggressive form of breast cancer.
During the four-year Ella Binational Breast Cancer Study, which was funded by National Institutes of Health/National Cancer Institute, scientists assessed the association between reproductive factors and tumors subtypes in 1,041 Mexican and Mexican-American female cancer patients.
Breast Cancer Subtypes
The study looked at the occurrence of three tumor subtypes: luminal A, HER2 and triple negative. The luminal tumor starts in the inner cell lining of the mammary ducts and is most common. This group includes tumors that are Estrogen receptor (ER) positive and Progesterone receptor (PR) positive, but negative for HER-2. Patients with this subtype of cancer are likely to benefit from hormone therapy and may also benefit from chemotherapy. The HER2 is positive for human epidermal growth factor receptor 2, a protein shown to play a role in aggressive breast cancer. This subtype includes tumors that are ER negative and PR negative, but HER2 positive. HER2 positive breast cancers are likely to benefit from chemotherapy and treatment targeted to HER2.
Triple negative breast cancer (TNBC) is insensitive to some of the most effective therapies available for breast cancer treatment including HER2-directed therapy such as trastuzumab and endocrine therapies such as tamoxifen or the aromatase inhibitors because the patient lacks the estrogen receptor, progesterone receptor, and HER2. While this cancer typically responsive to chemotherapy it remains difficult to treat, and gives it one of the worst possible prognosis. Depending on the stage of the diagnosis, triple negative breast cancer can be particularly aggressive, and is more likely to recur than other subtypes of breast cancer.
Mexican descent
“We found that breastfeeding in women of Mexican descent is associated with triple negative breast cancer,” said Mar?a Elena Mart?nez, MPH, PhD, UC San Diego Moores Cancer Center Sam M. Walton Endowed Chair for Cancer Research and co-director of the Reducing Cancer Disparities research program and lead author of the study. “This was quite surprising. No other study has seen this correlation before. Most studies show health benefits of breastfeeding.”
The average age when women in the ELLA study gave birth to a first child was 23 years old. These women had an average of two to three children and were likely to breastfeed for long periods of time. “Based on existing research, primarily based on non-Hispanic white women, this reproductive pattern would be classified as low risk. Yet all of the women in the study developed breast cancer,” Mart?nez explained.
Study design
The Ella study enrolled breast cancer patients, 18 years old and older, at the University of Arizona Cancer Center, the University of Texas M.D. Anderson Cancer Center and three sites in Mexico ? the Universidad de Sonora, the Instituto Tecnol?gico de Sonora and the Universidad de Guadalajara.
The study showed that patients of Mexican descent who breastfed for 12 months or more were more than twice as likely to have triple negative breast cancer. They were younger at diagnosis and younger during their first full-term pregnancy. Patients who had three or more children were also more likely to have triple negative breast cancer. Martinez said that it is important to note that prior studies, mainly in non-Hispanic white women, have shown that these reproductive characteristics reduce the risk of breast cancer overall, possibly due to effects on the more common, better prognosis, of luminal A cancers.
Giving the right message
“Our results are both puzzling and disconcerting because we do not want to give the wrong message about breastfeeding,” Mart?nez noted. “If you treat breast cancer as one disease, breastfeeding is beneficial to both mother and baby. That should not be dismissed.”
Mart?nez also noted that the most important takeaway from this report is that the scientific community needs to do further research into populations with unique risk-factor patterns that might benefit from different screening or prevention approaches. “The observations made in the ELLA study need to be replicated in populations with similar reproductive profiles to determine if the results are due to common biologic factors or specific genetic or environmental factors of the women in the this study,” she concluded.
For more information:
[1] Colditz GA, Baer HJ, Tamimi RM. Breast cancer. In: Schottenfeld D, Fraumeni JF, editors. Cancer Epidemiology and Prevention. 3rd ed. New York: Oxford University Press, 2006.
[2]Russo J, Moral R, Balogh GA, Mailo D, Russo IH. The protective role of pregnancy in breast cancer. Breast Cancer Research 2005; 7(3):131?142.[Article][PubMed]
[3]Britt K, Ashworth A, Smalley M.Pregnancy and the risk of breast cancer. Endocr Relat Cancer. 2007 Dec;14(4):907-33.[Article][PubMed]
[4] Martinez ME, Wertheim BC, Na
tarajan L, Schwab R, Bondy ML, Daneri-Navarro A, Meza-Montenegro MM,et al.Reproductive Factors, Heterogeneity, and Breast Tumor Subtypes in Women of Mexican Descent. Cancer Epidemiol Biomarkers Prev. 2013 Aug 15. [Epub ahead of print][Article][PubMed]
Photo: Maria Elena Martinez, M.P.H., Ph.D.Courtesy: UC San Diego School of Medicine. “Lactation may be linked to aggressive cancer in Mexican women.”
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