Breast Pain
Prevalence studies indicate that 68% of premenopausal women suffer from cyclic breast pain, and up to 22%, or eight million women in the United States, have cyclic breast pain that is moderate-to-severe in nature for two weeks or longer during their menstrual cycles. In fact, one study conducted by Dr. Deborah Ader of the National Institutes of Health indicates that the number may be as high as 11 million premenopausal women.
While mild premenstrual discomfort lasting one-to-four days per month is considered normal, moderate-to-severe cyclic breast pain is a more prolonged and debilitating disorder which can cause significant pain and anxiety as well as unnecessary cost to women and the healthcare system. Case-control studies1 and population-based phone surveys2 report that women with cyclic breast pain have more frequent mammograms12,13, biopsies12, and needle aspirations12, as well as increased patient concern and anxiety. As a chronic condition, moderate and severe breast pain disrupts the daily life activities of many women. In a clinic-based survey of 1171 women, 48% of women reported that cyclic breast pain interfered with sexual activity, 37% reported detrimental effects on physical activity, 12% an interruption of social activities and 8% an interference in work or school.3
In fact, although a poorly discussed and poorly treated condition, breast pain is one of the most common breast disorders experienced by women.4 In a survey of working women, 21% described having severe breast pain, but fewer than half had reported this pain to a physician.5
When women do seek medical attention for cyclic breast pain, it is often because of concerns about cancer.6,7,8 Cyclic breast pain is rarely a symptom of cancer9, however, and once a negative mammogram is evaluated, the physician is left with no clear standard of care to treat the patient. Decisions regarding treatment of breast pain are often made by the OB/GYN or, in severe cases, the breast surgeon, and require balancing the need for symptom relief against the likelihood of adverse effects from current treatments, such as danazol, bromocriptine or tamoxifen. Danazol, the only medication approved by the FDA for the treatment of breast pain, results in adverse effects in 30% of patients.10 These adverse effects are primarily androgenic and include acne, hair loss, decrease in voice pitch, weight gain, headache and amenorrhea. As a result, the patient is often told to "live with the pain."
Breast pain is actually related to fluctuating hormone levels. BHR-Pharma is investigating a transdermal therapy called Afimoxifene gel (4-hydroxytamoxifen gel). Results of a Phase 2 clinical trial of Afimoxifene gel indicate that the treatment was well tolerated and showed a statistically significant reduction in cyclic breast pain. In this trial, headaches were the most common side effect, which were in general mild and similar across treatment groups.
Afimoxifene (4-hydroxytamoxifen or 4-OHT), the active ingredient in Afimoxifene gel, is an estrogen inhibitor that cannot be delivered orally due to high first-pass liver metabolism. Afimoxifene (4-OHT) is one of the most active metabolites of tamoxifen. Tamoxifen, an orally administered, systemic estrogen receptor antagonist, is the most commonly prescribed adjuvant treatment for breast cancer. Tamoxifen is also recommended as chemoprevention in women at high risk for breast cancer and has been shown to reduce the risk of benign breast disease in premenopausal women11. The full therapeutic potential of oral tamoxifen for benign breast disease, however, is limited by its pharmacokinetics and safety. Most significant to the premenopausal population is the premature onset of menopausal symptoms, such as amenorrhea, hot flushes and night sweats. Two of the other most widely known risks with oral tamoxifen therapy are increased risk of thromboembolic events and endometrial cancer, but these serious adverse effects have not been noted in premenopausal women under age 50. Many of the side effects of oral tamoxifen therapy are due to first-pass liver metabolism and systemic exposure.
The disadvantages of systemic tamoxifen therapy for the treatment of benign breast disease could potentially be overcome by delivering its potent 4-OHT metabolite directly to the breast tissue, and thus avoiding or minimizing systemic exposure.
BHR-Pharma has formulated Afimoxifene gel for transdermal delivery to the breast tissue using Enhanced Hydroalcoholic Gel Technology (EHG™) which enables the percutaneous absorption of certain drugs, such as Afimoxifene, that cannot be delivered orally. Afimoxifene gel is applied daily by the patient to the surface of the breast. In previous clinical trials, Afimoxifene gel has been shown to be biologically active in the breast tissue, while having systemic exposure in the plasma that is nine times lower than that of oral tamoxifen.12
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9 Preece PE, Baum M Mansel RE, et al. Importance of mastalgia in operable breast cancer. BMJ (Clin Res Ed). 1982; 284: 1299-1300.
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11 Tan Chiu, E, et al. Effects of tamoxifen on benign breast disease in women at high risk for breast cancer. JNCI. 2003; 95: 302-307
12 Rouanet P, Linares-Cruz G, Dravet F et al. Neoadjuvant Percutaneous 4-Hydroxytamoxifen Decreases Breast Tumoral Cell proliferation: A Prospective, Controlled, Ramdomized Study Comparing 3 Doses of 4-OHT Gel to Oral Tamoxifen. 2003 San Antonio Breast Cancer Symposium, Poster Session.
