Gynecologic Oncology

Findings raise new concerns about birth control safety

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Birth Control

Since the 1960s, when the birth control pill made its debut, contraceptives have played a major role in family planning. So when researchers discovered that women taking hormone-based birth control had a higher incidence of breast cancer, making the contraceptives safer became an important public health priority. Many experts believed they found a solution in options with far lower doses of estrogen, a hormone long linked to breast cancer occurrence. But a new study suggests that low-dose contraceptives have not had the impact doctors expected, and experts are urging women to talk to their doctors about the implications for their breast health, even though the overall risk remains relatively small.

The study, published in December in The New England Journal of Medicine, followed 1.8 million women for an average of about 11 years, finding that those on hormonal contraception had a 20 percent higher risk of breast cancer—no matter the dose of estrogen—than women who never used those birth control methods. It’s an important discovery, especially with an estimated 140 million women across the globe using some form of hormonal contraception. Now, the findings have experts taking a closer look at another hormone singled out by the study: progestin.

Hormonal birth control methods, which include pills, patches, shots, and vaginal rings or intrauterine devices, prevent pregnancy by delivering combinations of synthetic estrogen and progestin, or just progestin alone, into the body. Estrogen and progestin stop the ovaries from releasing eggs, thicken the cervical mucus to keep sperm from entering the uterus, and thin the lining of the uterus to prevent implantation. Because high estrogen levels may cause certain types of cancer cells to grow, experts have long believed estrogen was the main hormonal culprit linking the contraceptives to an increased breast cancer risk, says Justin Chura, MD, Chief of Surgery and Director of Gynecologic Oncology and Robotic Surgery at our hospital near Philadelphia.

“ Now we see that the progestin plays a role, as well in the risk. We definitely had a faulty assumption going in.” – Justin Chura, MD – Chief of Surgery and Director of Gynecologic Oncology

There’s no reason for panic, Dr. Chura says, since the risk of breast cancer from hormonal contraception remains relatively small for most women. “Oral contraceptives are still a great class of drugs,” he says. “There is no ‘free lunch’ in terms of any of the medications we prescribe. There are always risks and benefits.” Such risks for hormonal contraception include blood clots, strokes and heart attacks. Benefits typically include a reduced risk of other types of cancer, including ovarian and endometrial cancers, as well as lighter or more regulated menstrual cycles, and, of course, help with family planning.

But each woman should weigh her individual risks, Dr. Chura says. Because breast cancer risk increases with both age and the length of time hormonal contraceptives are used, women already at higher risk for breast cancer, and those who are older and no longer planning to have children, may want to consider switching to a hormone-free birth control method, such as a diaphragm or condoms. Older women who have been on hormone-based birth control for a number of years may also consider getting screened for breast cancer at the earliest age that guidelines recommend. And women who are on progestin-only contraception may consider talking to their doctor about changing their birth control method.

For women in their 20s, the benefits of hormonal contraception often outweigh the risks, but medical and family histories still come into play. “Even if you’re 25, if you’re a BRCA mutation carrier, it makes sense for you to factor in the breast cancer risk that comes with hormonal contraception because you’re already at a higher risk for breast cancer than people without that mutation,” Dr. Chura says. Oral contraceptives, though, are also known to decrease the risk of ovarian cancer for patients with and without a BRCA mutation.

Despite the new findings, Dr. Chura says women should talk to their doctor before making any changes to their birth control. “Now women can have more educated discussions with their doctors,” he says.

Weight Affects Survival in Cervical Cancer

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Overweight and underweight women with cervical cancer did not live as long as their normal-weight counterparts, according to the results of a retrospective cohort study.

The median overall survival time in overweight/obese women was 6 months shorter than in women of normal weight (22 versus 28 months). For underweight women, median overall survival time was cut in half (14 versus 28 months), reported Leslie Clark, MD, of the University of North Carolina at Chapel Hill, and colleagues.

Being overweight or underweight, as determined by body-mass index (BMI), was also associated with worse recurrence-free survival and disease-free survival, Clark and colleagues said in Gynecologic Oncology.

“In understanding the effect of BMI on cervical cancer outcomes, it is important to recognize that both extremes of weight appear to negatively impact survival. Optimizing weight in cervical cancer patients may improve outcomes in these patients.”

The study included 632 women diagnosed with cervical cancer and treated at the university from 2000 to 2013. Their BMI was calculated using height and weight measurements taken at initial presentation to the oncology clinic. Four percent of the women were underweight (n=24), 30% were normal weight (n=191), and 66% were overweight or obese (n=417).

The investigators looked for connections between BMI at time of presentation and survival, controlling for factors including age, race, smoking, cancer stage, tumor grade, and histology.

Being overweight or obese was associated with significantly reduced median overall survival time compared with normal weight (22 versus 28 months; P=0.031). For underweight women, the reduced survival time was more dramatic (14 versus 28 months;P=0.018).

Compared with for normal-weight women, median recurrence-free survival time was also significantly shorter in obese/overweight women (7.6 versus 25 months; P=0.009) and in underweight women (20 versus 25 months; P=0.026).

There was a borderline-significant trend toward worse disease-specific survival in overweight/obese women compared with those of normal weight (22 versus 28 months; P=0.089). For underweight women, the difference was significant (14 versus 28 months; P=0.042).

Potential Underlying Mechanisms

“A potential unifying hypothesis connecting both extremes of weight to poor cancer prognosis is chronic systemic inflammation,” Clark and colleagues wrote. “Both patients with cancer cachexia/sarcopenia and overweight/obese patients are in a heightened inflammatory state, which may lead to increased cell proliferation and inhibition of apoptosis.

“However, this is likely not the only mechanism of poor outcomes. Co-morbid medical conditions might account for some of the differences in survival, particularly in morbidly obese patients.”

 Limitations of the study included its retrospective nature and the fact that all patients were treated at a single institution, which means the results may not be broadly generalizable, the investigators said.

“This study shows that the extremes of weight are detrimental to survival in women with cervical cancer, and further investigation regarding the cause of poor prognosis is warranted. Providers should optimize weight in underweight and overweight/obese patients to attempt to improve outcomes in these women. Interventions that target nutritional counseling and physical activity should be explored in these populations,” Clark and colleagues concluded.

Corroborating Evidence

A similar study presented at the recent Society of Gynecologic Oncology meeting corroborates the results of Clark et al.

That study, conducted by Aida Moeini, MD, of the University of Southern California, Los Angeles, and colleagues, examined the effect of weight change over time on disease-free survival rates in 665 women with endometrial cancer.

At 5 years, disease-free survival had fallen well below 50% for women who had either lost or gained 15% or more of their body mass. For women in the smallest weight-change category, those who had lost or gained less than 7.5% of body mass, disease-free survival was about 80%, Moeini and colleagues reported.

“Our results demonstrated that endometrial cancer patients continued to gain weight after hysterectomy, and post-treatment weight change had a bi-directional effect on survival outcome.”