Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers

Abstract

Early age at first birth and multiparity have been associated with a decrease in the risk of breast cancer in women in the general population. We examined whether this relationship is also present in women at high risk of breast cancer due to the presence of a mutation in either of the 2 breast cancer susceptibility genes, BRCA1 or BRCA2. We performed a matched case-control study of 1,260 pairs of women with known BRCA1 or BRCA2 mutations, recruited from North America, Europe and Israel. Women who had been diagnosed with breast cancer were matched with unaffected control subjects for year of birth, country of residence, and mutation (BRCA1 or BRCA2). Study subjects completed a questionnaire detailing their reproductive histories. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. Among BRCA1 carriers, parity per se was not associated with the risk of breast cancer (OR for parous vs. nulliparous 5 0.94; 95% CI 5 0.75-1.19; p 5 0.62). However, women with a BRCA1 mutation and 4 or more children had a 38% decrease in breast cancer risk compared to nulliparous women (OR 5 0.62; 95% CI 5 0.41-0.94). In contrast, among BRCA2 carriers, increasing parity was associated with an increased risk of breast cancer; women with 2 or more children were at approximately 1.5 times the risk of breast cancer as nulliparous women (OR 5 1.53; 95% CI 5 1.01-2.32; p 5 0.05). Among women with BRCA2 mutations and who were younger than age 50, the (adjusted) risk of breast cancer increased by 17% with each additional birth (OR 5 1.17; 95% CI 5 1.01-1.36; p 5 0.03). There was no significant increase in the risk of breast cancer among BRCA2 carriers older than 50 (OR for each additional birth 5 0.97; 95% CI 5 0.58-1.53; p 5 0.92). In the 2-year period following a birth, the risk of breast cancer in a BRCA2 carrier was increased by 70% compared to nulliparous controls (OR 5 1.70; 95% CI 5 0.97-3.0). There was a much smaller increase in breast cancer risk among BRCA2 carriers whose last birth was 5 or more years in the past (OR 5 1.24; 95% CI 5 0.79-1.95). A modest reduction in risk of breast cancer was observed among BRCA1 carriers with 4 or more births. Among BRCA2 carriers, increasing parity was associated with a significant increase in the risk of breast cancer before age 50 and this increase was greatest in the 2-year period following a pregnancy. ' 2005 Wiley-Liss, Inc.Key words: parity; breast cancer; BRCA mutation The lifetime risk of breast cancer among carriers of mutations in BRCA1 or BRCA2 is approximately 80%, 1,2 but individual risks may vary due to the effect of modifying factors.3 Reproductive factors have long been known to be important in the risk of breast cancer in the general population. 4 In an earlier study, we reported that increasing parity was associated with an increased risk of early-onset (< 40 year of age) breast cancer in both BRCA1 and BRCA2 carriers.5 However, the size of this study was small (189 matched pairs with BRCA1 mutations and 47 matched pairs with BRCA...

Cancer risks among BRCA1 and BRCA2 mutation carriers

“…In BRCA1 and BRCA2 carriers, parity effects may also be age dependent. While an early report suggested that parity may increase risk for early onset (o40 years) breast cancer in BRCA1 carriers (Narod, 2002a), a larger retrospective study of 1260 carrier pairs by the same group did not confirm this finding, and even observed decreased breast cancer risk in BRCA1 carriers with Xfour children (OR ¼ 0.62, 95% CI 0.41 -0.94, vs nulliparous carriers) (Cullinane et al, 2005). In BRCA2 carriers, this study found that parity caused a borderline increase in risk for breast cancer before age 50 years (OR ¼ 1.17 for each pregnancy, 95% CI 1.01 -1.36) (Cullinane et al, 2005).…”

“…While an early report suggested that parity may increase risk for early onset (o40 years) breast cancer in BRCA1 carriers (Narod, 2002a), a larger retrospective study of 1260 carrier pairs by the same group did not confirm this finding, and even observed decreased breast cancer risk in BRCA1 carriers with Xfour children (OR ¼ 0.62, 95% CI 0.41 -0.94, vs nulliparous carriers) (Cullinane et al, 2005). In BRCA2 carriers, this study found that parity caused a borderline increase in risk for breast cancer before age 50 years (OR ¼ 1.17 for each pregnancy, 95% CI 1.01 -1.36) (Cullinane et al, 2005). In a case-only study, young age at first pregnancy delayed onset of breast cancer in carriers (King et al, 2003), and a retrospective study of 1601 carriers found that in women over 40 years of age, each full-term pregnancy reduced breast cancer risk by 14% (95% CI 6 -22%).…”

Relationships between Breast Cancer and Common Non-Communicable Disease Risk Factors: an Ecological Study

“…However, many type of fruits for example orange and lemon have B and C vitamins and antioxidant elements that may decrease or prevente BC incidences (Blount, 2002;Azizi, 2003;Cullinane, 2005;Greene, 2006). Our incidences and use of fruits that is in agreement with some studies (Blount, 2002;Azizi, 2003).…”

Modifiers of risk of hereditary breast cancer

“…The effect of pregnancy on hereditary breast cancer risk appears to differ for BRCA1 and BRCA2 carriers. In a large matched case-control study, Cullinane et al (2005) reported that the risk of breast cancer did not decrease with pregnancy in BRCA1 carriers until four births were reached, after which there was only a modest protective effect. However, among BRCA2 carriers, there was a statistically significant increase in breast cancer risk with each additional pregnancy (OR ¼ 1.17, 95% CI: 1.01-1.36; P ¼ 0.03).…”