Managing Menopausal Symptoms in Breast Cancer Patients

J. Michael Dixon, MD

Common menopausal symptoms in patients with breast cancer include hot flashes, night sweats, sleep disturbances, and impaired sexual functioning. In one of his presentations at the 30th Annual Miami Breast Cancer Conference®, J. Michael Dixon, MD, offered a number of effective options for clinicians to help patients better manage these symptoms and improve their quality of life.

Dixon is professor of Breast Surgery and consultant breast surgeon at the Western General Hospital in Edinburgh, Scotland. He is also clinical director of the Breakthrough Breast Cancer Research Unit at the University of Edinburgh. His discussion focused on two particularly troubling aspects of menopause for patients with breast cancer—hot flashes and vaginal dryness.

Hot flashes are much more prevalent in breast cancer patients and survivors than in healthy women, and occur at a younger age. Dixon told his audience that while lifestyle adaptations and alternative therapies can help some patients, other options are needed, especially for patients whose hot flashes are severe.

Among the pharmacologic treatments which traditionally have been used, Dixon said, are the selective serotonin reuptake inhibitor (SSRI) antidepressants paroxetine, venlafaxine, and mirtazapine; however, they can have significant side effects and can result in switching one side effect for another, he added.

“The best drug around in the SSRI group at the moment is citalopram,” Dixon said. He pointed to encouraging results from a randomized, phase III clinical trial, involving 254 women receiving 10, 20, or 30 mg of the drug or placebo, and citalopram was found to be effective and well-tolerated (J Clin Oncol. 2010;28(20):3278-3283). He said 10 mg of the drug proved equally effective in patients taking either tamoxifen or an aromatase inhibitor (AI) and produced relatively few side effects. The 20 mgdose had greater mood improvement and other antidepressant effects, he added.

Other drug treatments for hot flashes include gabapentin and clonidine, which, he said, are somewhat effective, but these also can produce side effects, including drowsiness.

Dixon said progestins, such as megestrol acetate and medroxyprogesterone acetate, are the most effective in treating hot flashes associated with menopause. The 20-mg daily dose of megestrol is preferred, he said, citing a phase III trial comparing the 20-mg dose with 40 mg or placebo (J Clin Oncol. 2008;26(10):1650-1656). This trial found a greater reduction in hot flashes in the 20-mg versus 40-mg cohort, 65% and 48%, respectively, and more side effects were associated with the 40-mg dose. He added that these drugs tend to be more efficacious in women >50 years of age.

He noted that safety concerns with these medications are different in breast cancer patients who are on anti-hormonal drugs. “When a patient is on an AI or tamoxifen, there are less likely to be concerns regarding recurrence, and there are certainly few reports of recurrence on treatment.”

Researchers have also examined reduced doses of tamoxifen to treat hot flashes. A randomized, double-blind trial testing 1- and 5-mg daily doses in comparison with the usual 20-mg dose, found expression of Ki-67 decreased in all three tamoxifen groups (J Natl Cancer Inst. 2003;85(11):779-790). The lower dose has other benefits, including a reduced risk of deep vein thrombosis and improved compliance, Dixon noted. “One of the things I will often do is to try and get patients on lower doses, because the dose reduction definitely improves their quality of life, and they get fewer hot flashes.”

Vaginal dryness and dyspareunia also are very common in women on AIs, Dixon explained. Clinicians may recommend lubricants to treat these conditions, and he stressed that not all water-based products are the same, noting that iso-osmotic and moderately hyperosmotic lubricants have been found to be more effective and less irritating.

Topical anesthetics that may provide relief, he said, include 5% lidocaine ointment for dyspareunia and topical gabapentin cream (6%), and he would like to see further studies of these treatments in breast cancer patients.

“The big issue is hormonal therapy,” Dixon said, and what hormonal therapies are safe for use in the vagina. “The art of medicine,” Dixon said, “is balancing the benefits with the harms.”

Hormonal agents include estradiol vaginal tablets (Vagifem) or rings (Estring), as well as estrogen or testosterone creams. He cited a small study which found vaginal estradiol to be contraindicated in postmenopausal women on adjuvant AIs (Ann Oncol. 2006;17(4):584-587), which he said has influenced many oncology professionals against its use. Another small study compared estrogen absorption in patients using either Vagifem (n = 4) or Estring (n = 3) (J Clin Oncol. 2012;24(8):e128- 129). In this study, he said, estradiol levels remained relatively stable with the Estring. Dixon called for more studies of these formulations in breast cancer patients, as well.