Abstract
Reproductive history and exogenous hormonal exposures are acknowledged risk factors for breast cancer in the general population. In women at increased breast cancer risk for genetic predisposition or positive family history, data regarding these risk factors are limited or conflicting, and recommendations for these categories are unclear. We evaluated the characteristics of reproductive life in 2522 women at increased genetic or familial breast cancer risk attending our Family Cancer Center. Breast cancers in BRCA mutation carriers were more likely to be hormone receptor negative, diagnosed at 35 years or before and multiple during the lifetime than tumors in women at increased familial risk, while the distribution of invasive cancers and HER2 positive tumors was similar in the different risk groups. At least one full-term pregnancy (HR 0.27; 95% CI 0.12–0.58; p = 0.001), breastfeeding either less (HR 0.24; 95% CI 0.09–0.66; p = 0.005) or more (HR 0.25; 95% IC 0.08–0.82; p = 0.022) than one year and late age at menopause (HR 0.10; 95% CI 0.01–0.82; p = 0.033) showed to be protective factors in BRCA mutation carriers, while in women at increased familial risk early age at first full-term pregnancy (HR 0.62; 95% IC 0.38–0.99; p = 0.048) and late menarche (HR 0.61; 95% CI 0.42–0.85; p = 0.004) showed to be the main protective factors. Finally, for the entire population, combined hormonal contraceptives demonstrated to do not increase breast cancer risk. The results of our study suggest that women at high familial risk and mutation carries develop tumors with different clinical-pathological characteristics and, consequently, are influenced by different protective and risk factors.
Highlights
Breast cancer (BC) represents the most common form of cancer and the leading cause of cancer death among women worldwide, with an estimated 1.7 million cases and 521,900 deaths in 2012
At least one fullterm pregnancy (HR 0.27; 95% CI 0.12–0.58; p = 0.001), breastfeeding either less (HR 0.24; 95% CI 0.09–0.66; p = 0.005) or more (HR 0.25; 95% IC 0.08–0.82; p = 0.022) than one year and late age at menopause (HR 0.10; 95% CI 0.01–0.82; p = 0.033) showed to be protective factors in BRCA mutation carriers, while in women at increased familial risk early age at first full-term pregnancy (HR 0.62; 95% IC 0.38–0.99; p = 0.048) and late menarche (HR 0.61; 95% CI 0.42–0.85; p = 0.004) showed to be the main protective factors
1541 (61%) were at High Risk (HR) with a mean age of 52 ± 13 years and 868 (34%) women were at Intermediate Risk (IR) with a mean age of 52 ± 12 years, according to the Modena criteria
Summary
Breast cancer (BC) represents the most common form of cancer and the leading cause of cancer death among women worldwide, with an estimated 1.7 million cases and 521,900 deaths in 2012. In the general population, acknowledged risk factors for BC are aging, white race, reproductive history (i.e. early menarche, late menopause, nulliparity, late age at first birth, no breastfeeding), exposures (i.e. exogenous hormones like combined hormonal contraceptives (CHCs) or hormone replacement therapy), alcohol, tobacco smoking, overweight and obesity, lack of exercise, dense breast tissue, previous chest radiation, precancerous lesions, personal history of BC, family history and mutations in BC predisposition genes (BRCA1, BRCA2, PALB2, PTEN, CHEK2, etc.) [2,3,4,5,6,7,8,9,10,11,12,13]. For what concerns women at increased familial risk with unknown mutation status, the data available are even more limited and conflicting
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