Breast Cancer Survivors Have Specific Gynecological Needs

Tara Haelle

May 06, 2021

Sexual dysfunction is a common problem among breast cancer survivors, but it's also an issue inadequately addressed by either ob/gyns. or hematologists and oncologists, according to Erin Keyser, MD, the program director of the San Antonio Uniformed Services Health Education Consortium. Keyser discussed management of sexual dysfunction and a variety of other issues frequently faced by women who have survived breast cancer at the at the 2021 virtual meeting of the American College of Obstetricians and Gynecologists.

"Despite the fact that no specialty is better qualified to render care for this consequence of cancer treatments, many obstetrician-gynecologists feel uncomfortable or ill-equipped to address sexual pain in women affected by cancer," Keyser quoted from a 2016 article in Obstetrics & Gynecology about the sexual health of women affected by cancer. As a breast cancer survivor herself, Keyser said hematologists and oncologists are even less equipped to discuss sexual health, "so oftentimes patients get punted between their hem-onc and their gyn," with each telling the patient to ask the other specialist.

"There's plenty of data in chronic health disease that maintaining sexual function for women is an indicator of the overall quality of life and that many women really don't want to bring this up," Keyser told attendees, so the onus is on the ob/gyn. to bring it up.

The effects of breast cancer treatment can impact women's body image, fertility, menopause, sexual function, osteoporosis, and cardiovascular disease, but the bulk of Keyser's talk focused on sexual health and bilateral salpingo-oophorectomy (BSO).

Lauren Streicher, MD, a clinical professor of obstetrics and gynecology at Northwestern University, Chicago, thought Keyser's talk was useful for the general gynecologist but had some concerns about a few parts.

"She gave a very thoughtful analysis of whether someone should have their ovaries removed or not in a breast cancer diagnosis, " Streicher said in an interview. "I would have liked to hear more about the consequences of an early menopause in women in terms of heart health, bone health, and cognitive function."

Keyser noted that her talk pertained mostly to survivors of estrogen receptor (ER)–positive breast cancer since that population tends to struggle most with side effects of treatment. The most common medications used in this population are tamoxifen and aromatase inhibitors – such as anastrazole, letrozole, and exemestane – and these medications can affect management of different concerns.

Current Guidance on Ovarian Removal

For women with a BRCA mutation, ACOG clinical guidance already exists regarding BSO. For other women, the complementary TEXT and SOFT trials changed the management of breast cancer treatment in premenopausal women, Keyser said.

Before these trials, postmenopausal hormone receptor–positive women began aromatase inhibitors and premenopausal HR-positive women began tamoxifen. These trials found that premenopausal women with HR-positive early breast cancer were less likely to experience recurrence when receiving adjuvant treatment with exemestane plus ovarian suppression compared to tamoxifen plus ovarian suppression. Ovarian suppression was achieved by either GnRH agonist injections, surgical removal of the ovaries, or radiation therapy to the ovaries.

The side effects of these treatments included hot flushes (92%), depression (87%), musculoskeletal symptoms (89%), vaginal dryness (52%), decreased libido (45%), dyspareunia (31%), osteoporosis (39%), insomnia (58%), and fatigue (61%). These are all quality of life concerns, Keyser said, and these findings raise questions about the consequences of long-term ovarian suppression. Findings from the Nurses' Health Study showed that BSO before age 47.5 years resulted in lower mortality from ovarian cancer and breast cancer but was linked in women under 50 to increased all-cause mortality and mortality from coronary heart disease, lung cancer, and colorectal cancer, compared with ovarian conservation. Further, 74% of women who undergo risk-reducing BSO experience sexual dysfunction.

The bottom line, Keyser said, is that "premature removal of ovaries is not completely benign." Her own recommendation is to follow ACOG guidance for women with BRCA mutations and, for women aged under 35 years, use ovarian suppression for 5-10 years, after which ovarian function may resume along with improved quality of life. In women aged over 40, remove ovaries since, after 5-10 years of treatment, there's likely no benefit of retaining ovaries.

Addressing Sexual Health

Dyspareunia affects up to 45% of cancer survivors, Keyser said, and multiple treatment options exist for breast cancer survivors. The therapies she discussed included lubricants, moisturizers, local vaginal estrogen, DHEA, ospemifene, and CO2 laser therapy.

Though Keyser briefly touched on vaginal lubricants and moisturizers, Streicher was disappointed that Keyser did not clearly define and differentiate between lubricants and moisturizers or mention hyaluronic acid products. Streicher also disagreed with the way Keyser represented the benefits of coconut oil as a lubricant. "Oils are not condom compatible and are known to potentially increase the risk of infection, and not just from poor handwashing," Streicher said.

Small retrospective studies support the safety of topical vaginal estrogen in breast cancer survivors, Keyser said, and the 10-mcg Vagifem tablet and vaginal estradiol ring appear to have the lowest systemic absorption. ACOG guidance recommends that women taking aromatase inhibitors who don't respond to nonhormonal approaches may benefit from switching temporarily to tamoxifen with vaginal estrogen and then returning to aromatase inhibitors. However, Keyser said there's plenty of data to support using vaginal estrogen in patients taking aromatase inhibitors.

"I do feel that it's safe for patients, whether they're on tamoxifen or aromatase inhibitors, to take vaginal estrogen," Keyser said. "I usually stick with the estradiol vaginal ring or the estradiol tablet, and I base that on a patient's comfort with placing and removing a ring." She also, instead of asking the patient's hematologist-oncologist, simply notifies them of the treatment since most hematologist-oncologists are less familiar with the data.

Another effective option is vaginal DHEA/prasterone, which can significantly improve sexual desire, arousal, pain, and overall sexual function. Although breast cancer patients were included in early studies on DHEA, Intrarosa manufacturers excluded breast cancer patients in their Food and Drug Administration application, resulting in a package stating that "use of exogenous estrogen is contraindicated in women with a known or suspected history of breast cancer" and that "Intrarosa has not been studied in women with a history of breast cancer." While that's true for Intrarosa specifically, DHEA has been studied in breast cancer patients, Keyser said, so she expects to see more research in this area.

Ospemifene is another option for improving vulvovaginal atrophy but cannot be taken at the same time as tamoxifen. It has similar chemopreventive effects as tamoxifen in rat studies, but it's not as effective. It's a reasonable option in women with refractory genitourinary syndrome of menopause (GSM) who have completed their 5-10 years of adjuvant therapy and have no history of venous thromboembolism.

Keyser said CO2 laser therapy is still being studied for treating GSM, and current data have shown benefits for dyspareunia and vaginal dryness without documented harms. There have now been randomized, controlled trials; however, since it's not FDA approved, it's not covered by insurance and costs approximately $5,000 for three treatments.

Streicher was glad to see Keyser's discussion of the safety and types of local vaginal estrogen, "although she neglected to mention the 4-mcg vaginal suppository, Imvexxy, which has the lowest systemic absorption," Streicher said. Streicher also felt the inclusion of DHEA/prasterone and ospemifene were also important, especially since the latter is "underutilized in breast cancer patients."

The information provided on CO2 laser therapy, however, was problematic, Streicher said, given that long-term and randomized, controlled studies have now been published. Streicher also noted that two of the devices listed on the presentation slide, Thermiva and Voltiva, are radiofrequency, not laser devices.

Aside from these treatment options, the most consistent predictor of satisfying sexual experiences in women with breast cancer is the quality of their relationships, Keyser said, so couples counseling is recommended, and treatments in general are more effective with regularly sexual activity.

In discussing nonhormonal options for treating vasomotor symptoms, Keyser recommended venlafaxine, gabapentin, and low-dose paroxetine (though SSRIs and tamoxifen are contraindicated since they may reduce tamoxifen's efficacy).

These are all off label, Streicher said it was important to note, and she would have liked to have seen a mention of the development of KNdy neurokinin disrupters along with a more in-depth discussion about which lifestyle modifications and botanicals have been shown in randomized, controlled trials to mitigate vasomotor symptoms.

Keyser wrapped up with a few additional notes and takeaways:

  • The only safe reversible long-term option for contraception in HR-positive breast cancer survivors is the Paraguard IUD.

  • It's important to discuss fertility with breast cancer patients and survivors since a majority report unmet needs in this area.

  • Patients taking tamoxifen need to be sure to report any vaginal spotting or bleeding since it increases risk of endometrial cancer in postmenopausal women.

  • Screen for depression and anxiety.

  • Ask women about sexual health and hot flashes.

  • Ensure that they're getting bone screening.

  • A recommended resource is Living Beyond Breast Cancer.

Keyser had no disclosures. Streicher has consulted for Astellas Pharma and Church & Dwight, and she owns investments in InControl Medical and Sermonix Pharmaceuticals.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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