Cancer Treatment Today

Sequellae of treatment for breast cancer can affect the quality of life for many years after treatment. Breast cancer patients often suffer menopausal symptoms, which include vaginal dryness. This distressing symptom is often treated with topical estrogen or progesterone creams; however, there remains a concern about absorption of estrogen into the body and its effect on breast cancer. Many patients are already on tamoxifen. In a group that is treated with tamoxifen, it would appear that most systemic effect would be negated by the tamoxifen’s anti-estrogen blockade but the question remains hotly debated. In regards to systemic estrogens, which are given by mouth, several observational studies and systematic reviews suggest no greater risk for breast cancer recurrence among breast cancer survivors treated with hormone replacement therapy(HRT). While systemic estrogens are nevertheless generally avoided because of an abundance of caution following estrogen receptor-positive breast cancer, vaginal estrogens in the form of creams or ointments are widely used to treat symptoms of atrophic vaginitis(dryness and pain form intercourse). Small retrospective studies in breast cancer patients suggest that vaginal estrogens do not adversely affect life expectancy. Similarly, vaginal estrogens were permitted in the placebo-controlled MA.17 trial of letrozole as extended adjuvant therapy following 5 years of tamoxifen without seeming to interfere with the observed efficacy of letrozone and tamoxifen.

A recent review(Hickey et al, 2008) concluded: “Ultimately, the decision to take estrogen for severe menopausal symptoms should rest with the patient who is fully informed regarding the potential adverse effects on disease prognosis. A benefit of multidisciplinary care is the ability to calculate individual patient recurrence risks and to use this information in decision making about treatment choices. In addition, if endocrine therapies are producing severe menopausal symptoms with relatively small benefits in terms of recurrence or survival, the multidisciplinary (MD) team may advise that these can reasonably be stopped or adjusted. For women with advanced breast cancer, the issues of quality of life(QOL) are paramount and Hormonal Therapy may be considered following discussion with the patient”.

Tamoxifen treatment is a complicating factor. In postmenopausal women, tamoxifen acts as a weak estrogen in the ovaries, uterus, and vaginal epithelium. On the other hand, Tajima et al reported on the anti-estrogenic effects seen in the vaginal epithelium of premenopausal women being treated with tamoxifen for infertility. Tamoxifen may block systemic effects on topical estrogenic preparations.Leydenin 2008 writes: “In some cases, local estrogen can be an alternative option, although patients must be carefully monitored, and many may not be comfortable with this approach.” Cochrane Systemic Review in 2004 said: “In women with a history of breast cancer, systemic estrogen or progesterone therapy is contraindicated because of the increased risk of breast cancer recurrence. Vaginal estrogen preparations often are used to treat symptoms of vaginal atrophy in these patients because of the low levels of systemic absorption.”

Therefore, use of estrogen preparation, albeit cautiously, is a reasonable option in this situation. You might think that if estrogens are a potential problem, vaginal androgens that suppress breast cancer growth would be safer. Still using androgens is problematic from the standpoint of evidence. AndroGel is an androgen containing cream that can be used vaginally. AndroGel, an androgen, is indicated for replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone, such as:

•Primary Hypogonadism (Congenital or Acquired) – testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter’s syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone levels and gonadotropins (FSH, LH) above the normal range.
•Hypogonadotropic Hypogonadism (Congenital or Acquired) – idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum levels but have gonadotropins in the normal or low range. Using it for vaginal dryness is an off-label use.

Using androgens for vaginal dryness is subject to a clinical trial: Vaginal Testosterone Cream For Atrophic Vaginitis in Women Taking Aromatase Inhibitors for Breast Cancer, NCT01122342. Results are not yet available, and I was not able to find published literature to support the safety of androgen gels for breast cancer patients. For this reason, androgen creams should for now be avoided.

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