Division of Medical Oncology A, Regina Elena Cancer Institute, Rome, Italy
*E-mail: pcarlini@iol.it
A 37-year-old premenopausal woman with relapsed breast cancer (BC) in the right supraclavicular nodes, after failed treatment with the combination luteinizing hormone releasing hormone-a (LHRHa; triptorelin) plus tamoxifen, was started on triptorelin 3.75 mg every 28 days plus letrozole 2.5 mg daily. Approximately 6 months after starting this therapy, she complained of a daily scalp hair loss while combing and progressively developed a diffuse non-scarring alopecia on her crown. There were no signs of virilization. A gynecological examination showed a normal looking vagina and uterine cervix. The uterus was normal in size and there were no ovarian masses at ultrasonography. Her previous medical history was unremarkable. She was not taking any other drug. Hematological parameters were normal. Blood examination ruled out pituitary or thyroid problems. There were no other possible causes that could induce alopecia, such as lupus erythematosus, HIV infection, secondary syphilis, or deficiencies of protein, iron, biotin or zinc (Table 1). A dermatologist prescribed topical minoxidil 2%, two local applications (2 ml) daily. Approximately 68 weeks after initiating minoxidil, hair loss stopped and hair regrowth became apparent.
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Consistent with the role of aromatase in avoiding androgen-mediated effects on androgen-dependent hair follicles is the observation that women taking AIs for the treatment of BC often experience androgenetic alopecia-like hair loss, as a consequence of the hormonal imbalance towards androgenization of the hair follicles. We could speculate that the LHRHa caused a fall in estradiol concentrations, leading to a relative hyperandrogenism. Additionally, the reduction of aromatase activity driven by letrozole may have resulted in a further relative increase in systemic and pilosebaceous testosterone available for conversion to DHT. This synergic action may explain why our patient did not show alopecia while taking triptorelin with tamoxifen. Moreover, minoxidil lengthened and enlarged the small vellus hairs and decreased shedding, highlighting the hypothesis of a relative hyperandrogenism as the cause of alopecia. Female sex hormone-binding globulin (SHBG) levels are inversely correlated with the grade of alopecia [5]. In our patient, the SHBG levels were low, potentially due to the AI effect.
Considering the pivotal importance of pharmacological castration in premenopausal endocrine-responsive BC patients and the widespread use of AIs in the metastatic and, probably in the near future, adjuvant settings, potential alopecia should not be a determinant in making clinical decisions. However, oncologists must be aware of such atypical adverse events for treatment planning, in order to highlight its consequent distress and to provide psychological counseling, especially in young patients.
P. Carlini*, S. Di Cosimo, G. Ferretti, P. Papaldo, A. Fabi, E. M. Ruggeri, M. Milella & F. Cognetti
Division of Medical Oncology A, Regina Elena Cancer Institute, Rome, Italy (*E-mail: pcarlini@iol.it)
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