Oral Contraceptive Use and Risk of Early-Onset Breast Cancer in Carriers and Noncarriers of <i>BRCA1</i> and <i>BRCA2</i> Mutations

Milne, Roger L.; Knight, Julia A.; John, Esther M.; Dite, Gillian S.; Balbuena, Ronald; Ziogas, Argyrios; Andrulis, Irene L.; West, Dee W.; Li, Frederick P.; Southey, Melissa C.; Giles, Graham G.; McCredie, Margaret; Hopper, John L.; Whittemore, Alice S.

doi:10.1158/1055-9965.epi-04-0376

Cited by 137 publications

(90 citation statements)

References 37 publications

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“…Two recent studies based on early-onset breast cancer cases, including small numbers (o100) of carriers, found no general increase in breast cancer risk with OC use. One study found increased breast cancer risk only with teenage (o20 years) OC use (OR ¼ 1.53 (95% CI 1.17 -1.99) per year of use at age o20 years) (Jernstrom et al, 2005), and in the others there was even a suggestion of decreased breast cancer risk within BRCA1 carriers (OR ¼ 0.22, 95% CI 0.1 -0.49 for OC use of at least 1 year) (Milne et al, 2005). Altogether, these studies suggest that for breast cancer risk, OC have similar relative effects in carriers and non-carriers.…”

Section: Hormonal Exposures -Oral Contraceptives (Oc)mentioning

confidence: 98%

Cancer risks among BRCA1 and BRCA2 mutation carriers

2007

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BRCA1 and BRCA2 mutations increase breast and ovarian cancer risks substantially enough to warrant risk reduction surgery, despite variable risk estimates. Underlying this variability are methodological issues, and also complex genetic and nongenetic effects. Although many modifying factors are unidentified, known factors can already be incorporated in individualised risk prediction. BRCA1 and BRCA2 were identified as genes mutated in hereditary breast/ovarian cancer by genetic analysis in families with multiple cases of these malignancies. In the following decade, as BRCA1 and BRCA2 testing became more common in patients with a personal or family history of cancer, numerous studies assessed cancer risks in carriers of these mutations. These studies have resulted in variable risk estimates, leading to difficulties in defining risk figures that are clinically applicable to the individual patient. However, they illuminated the complexities that underlie risk prediction even in the context of a single gene with major effects on cancer predisposition. The emerging picture is that breast and ovarian cancer risks in BRCA1 and BRCA2 carriers are substantially higher than in the general population, but that they are considerably affected by nongenetic, environmental factors, and by additional genetic modifiers. BREAST AND OVARIAN CANCER RISK IN WOMENOriginal estimates of breast and ovarian cancer risks in carriers were based on the families used for positional cloning of the BRCA1 and BRCA2 genes, where all carriers had molecular testing, and all cancer diagnoses were validated. These families were chosen because they harboured multiple, early-onset cases, that is, they were essentially selected for high cancer risk. In the Breast Cancer Linkage Consortium (BCLC) families, by age 70 years, BRCA1 carriers had a breast cancer risk of 71% (95% CI 53 -82%) and an ovarian cancer risk of 47 -63% (Easton et al, 1995). BRCA2 carriers had a breast cancer risk of 84% (95% CI 43 -95%), and an ovarian cancer risk of 27% (95% CI, 0 -47%) (Ford et al, 1998). Many subsequent studies were case-based, that is, risk was estimated by analysis of family history in relatives of breast or ovarian cancer patients, often from hospital-based series (Antoniou et al, 2003). The design of these studies partially addressed the ascertainment bias inherent in studying highly selected, multiple-case families, but risk estimates were based on family history, rather than on testing carriers directly and validating their cancer status. With this design, misclassification can result from discrepancies between modelled vs true carrier status, and from errors in cancer reporting by relatives, a particularly common problem for ovarian cancer. In a meta-analysis of such case-based studies, by age 70 years, in BRCA1 carriers breast cancer risk was 65% (95% CI 51 -75%) and ovarian cancer risk was 39% (95% CI 22 -51%), and in BRCA2 carriers breast cancer risk was 45% (95% CI 33 -54%) and ovarian cancer risk was 11% (95% CI 4.1 -18%) (Antoniou et al, 2003). One s...

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Section: Hormonal Exposures -Oral Contraceptives (Oc)mentioning

confidence: 98%

Cancer risks among BRCA1 and BRCA2 mutation carriers

2007

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“…A population-based case-control study assessed COC use as a risk factor in Caucasian carriers and noncarriers of BRCA1 and BRCA2 mutations. 23 Use of low-dose COCs was not associated with increased risk of breast cancer in either BRCA2 mutation carriers or noncarriers. Furthermore, the results suggested a reduced risk of breast cancer in BRCA1 mutation carriers.…”

Section: -12mentioning

confidence: 90%

Efficacy and side‐effects of oral contraceptives

MacGregor¹

2017

Prescriber

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“…Notably, of the cases that used OCP in this study, more than 50% initiated OCP use before 1975, when the estrogen content of OCP was substantially higher than current formulations. However, a large multinational case-control study including 1156 breast cancer cases diagnosed under age 40 (of which 47 were BRCA1 carriers and 35 BRCA2 carriers) as well as 815 controls, did not demonstrate an increased risk of OCPassociated breast cancer (Milne et al, 2005). In fact, a decrease in breast cancer risk was seen in BRCA1 carriers using OCP for >12 months (OR 0.22, 0.10-0.49).…”

Section: Chemoprevention Of Ovarian Cancermentioning

confidence: 93%

Clinical management of BRCA1 and BRCA2 mutation carriers

Domchek

Weber

2006

Oncogene

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The cancer susceptibility genes BRCA1 and BRCA2 appear to be responsible for virtually all hereditary breast ovarian families, and a smaller subset of hereditary sitespecific breast cancer families. Fortunately, effective strategies have been developed to reduce the risk for the development of breast and ovarian cancer in women with BRCA1/2 mutations, making genetic testing for these mutations an important part of the management at women with a strong family history of these diseases. Here, we review the current evidence for risk reduction strategies and outline future research directions. Oncogene (2006) 25, 5825-5831. doi:10.1038/sj.onc.1209881Keywords: BRCA1; BRCA2; oophorectomy; breast cancer; ovarian cancer; management Management of ovarian cancer risk Prophylactic oophorectomyThe lifetime risk of ovarian cancer for women with BRCA1 mutations is estimated at 40-50% (Ford et al., 1994;Antoniou et al., 2003;King et al., 2003) and in those with BRCA2 mutations, at 10-20% (1999;Antoniou et al., 2003;King et al., 2003). We and others have shown conclusively that prophylactic oophorectomy (PO) in women with BRCA1/2 mutations reduces the risk of ovarian cancer by approximately 90% (Kauff et al., 2002;Rebbeck et al., 2002;Rutter et al., 2003;Domchek et al., 2006). Data with short-term follow-up also suggests that oophorectomy is associated with an improvement in breast cancer-specific survival, ovarian cancer-specific survival and overall survival (Domchek et al., 2006) (Figure 1). Table 1 reports the details of studies examining PO in BRCA1/2 mutation carriers. Rebbeck et al. (2002) examined 551 women from 11 centers in North America and Europe who either did (n ¼ 259) or did not (n ¼ 292) undergo PO, with a mean follow-up of over 8 years in each group. Eight PO subjects (3.1%) were diagnosed with ovarian cancer or primary peritoneal cancer at or following PO compared with 58 controls (19.9%). Six of the eight PO subjects diagnosed with ovarian cancer were diagnosed at the time of PO, all of which were stage I. After excluding these six cases, only two women (both with BRCA1 mutations) who underwent PO subsequently developed primary peritoneal cancer. Compared with women who did not undergo PO, the occurrence of post-PO ovarian cancer corresponded to a hazard ratio (HR) of 0.04 (95% confidence interval (CI): 0.01-0.16). In addition to this striking reduction in the risk of ovarian cancer, an approximately 50% breast cancer risk reduction after PO was also observed (HR ¼ 0.47; 95% CI: 0.29-0.77). In an another study with similar results, Kauff et al. (2002) identified 170 women with BRCA1/2 mutations who had not previously undergone PO, who then chose to either undergo ovarian cancer surveillance or undergo PO. During a mean follow-up of 24.2 months, ovarian cancer or primary peritoneal carcinoma was diagnosed in one of 98 women who chose to undergo PO compared to five ovarian or peritoneal cancers in the 72 women who chose surveillance. This risk reduction corresponded to a HR of 0.15 (95% CI: 0.02-1.31).Finally, ...

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Oral Contraceptive Use and Risk of Early-Onset Breast Cancer in Carriers and Noncarriers of BRCA1 and BRCA2 Mutations

Cited by 137 publications

References 37 publications

Cancer risks among BRCA1 and BRCA2 mutation carriers

Cancer risks among BRCA1 and BRCA2 mutation carriers

Efficacy and side‐effects of oral contraceptives

Clinical management of BRCA1 and BRCA2 mutation carriers

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