Saturday, May 31, 2014

Oral Contraceptives effect on Breast and Ovarian Cancer Risk

       In Megan and Christina's presentation, they discussed how the increased level of estrogen and progesterone during pregnancy causes breast tissue to differentiate and ultimately decreases risk of developing breast cancer. Because most combination birth control pills contain both estrogen and progesterone it made me curious about if the use of oral contraceptives can have similar effects of pregnancy and decrease risk of breast cancer. However, the information I found was opposite of what I had anticipated.
       Many studies have been conducted that support the notion that oral contraceptives increase one's risk of getting breast cancer. Though this is the opposite of my initial thought, it makes sense when you think about how early menarche and late menopause increase one's risk of getting breast cancer. These hormones cause differentiation in the breast tissue during and after pregnancy. However, increased levels of estrogen outside of pregnancy promotes DNA synthesis and cell proliferation. With increased cell proliferation there is a greater chance that mutations can occur. (1) Also, as Megan and Christina brought up in their presentation, it was seen that parous rats have a G1 phase twice as long as the virgin rats. Even though this extended G1 phase has not yet been proven in humans, it is an advantage that women just taking oral contraceptives would not have. Therefore, women taking oral contraceptives have increased cell proliferation due to the higher levels of hormones, without an extended G1 phase to prevent mutated cells from dividing.

Figure 1. Comparisons of relative risks for breast cancer(2)

       In 1996, the Cancer Epidemiology Unit at Oxford University analyzed data from 53,297 women with breast cancer and 100,239 women without breast cancer from around the world and examined use of oral contraceptives as a potential risk factor for breast cancer. The risk of developing breast cancer was found to be the highest in current users (1.24 [1.15-1.33], 2p<0.00001). The amount of risk gradually decreases with increasing amount of years since the end of use, until ultimately the risk disappears 10 years after stopping use(3). However, an interesting finding was that the tumors that were found in the women who had been using oral contraceptives were less advanced clinically than women who had never used oral contraceptives. The risk that the cancer had metastasized as opposed to localized tumors was found to be 0.88(0.81-0.95; 2p=0.002)(3). So, even though oral contraceptives increase one's risk of developing breast cancer, the cancer has a lower risk of metastasizing. 

       While the use of oral contraceptives increase the risk of breast cancer, they can decrease the risk of developing ovarian cancer in patients with BRCA1 or BRCA2 mutations. A case-control study performed by the Samuel Lunenfeld Research Institute examined oral contraceptive's and parity's effect on ovarian cancer risk of patients with BRCA1/2 mutations. They found that the use of oral contraceptives dramatically decreased the risk in patients with these mutations (BRCA1 0.56 [95% CI 0.45-0.71]; p<0.0001)(BRCA2 0.39 [0.23-0.66]; p=0.0004). An interesting finding was that although parity decreases risk of ovarian cancer in those with BRCA1 mutations by about the same amount as use of an oral contraceptive, it increases the risk in BRCA2 mutation carries (2.74 [1.18-6.41]; p=0.02). Though the results are significant, case-control studies are often subject to bias. In addition, the sample size of those with a BRCA1 mutation was 670 patients, while it was only 128 patients with BRCA2 mutations(4). This makes me skeptical about the BRCA2 findings, particularly parity increasing the risk of ovarian cancer. 

1. Conova, Susan. "Estrogens Role in Cancer ." Colombia University Health Sciences. N.p., 26 May 2003. Web. <>.

2. Reid, Robert L. "Hormonal Contraception and Breast Cancer: Keeping Perspective." JOGC (2007): 207-09. Web. 31 May 2014. <>.

3. Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53,297 women with breast cancer and 100,239 women without breast cancer from 54 epidemiological studies. Lancet 1996; 347(9017):1713–1727.\

4. Samuel Lunenfield Research Institute: Reproductive risk factors for ovarian cancer in carriers of BRCA1 or BRCA2 mutations: a case-control study. Lancet. N.p., 8 Jan. 2007. Web. 31 May 2014. <>.