Permanent Alopecia in Breast Cancer Patients: Role of Taxanes and Endocrine Therapies

Comment

Classification of Chemotherapy-Induced Hair Loss
Chemotherapy-induced alopecia is typically an anagen effluvium that is reversed within 6 months following the final course of chemotherapy. When incomplete regrowth persists, the patient is considered to have PCIA.¹ The pathophysiology of PCIA is unclear.

Traditional grading for chemotherapy-induced alopecia does not account for the patterns of loss seen in PCIA, of which the most common appears to be a female pattern with accentuated hair loss in androgen-dependent regions of the scalp.¹⁸ Other patterns include a diffuse type with body hair loss, patchy alopecia, and complete alopecia with or without body hair loss (Table).^3-8 Whether these patterns all can be attributed to chemotherapy remains to be explored.

Breast Cancer Therapies Causing PCIA
The main agents thought to be responsible for PCIA in breast cancer patients are taxanes. The role of endocrine therapies has not been well explored. Trastuzumab lacks several of the common side effects of chemotherapy due to its specificity for the HER2/neu receptor and has not been found to increase the rate of hair loss when combined with standard chemotherapy.^19,20 Although radiation therapy has the potential to damage hair follicles, and a dose-dependent relationship has been described for temporary and permanent alopecia at irradiated sites, permanent alopecia predominantly has been reported with cranial radiation used in the treatment of intracranial malignancies.²¹ The role of radiation therapy of the breasts in PCIA is unclear, as its inclusion in therapy has not been consistently reported in the literature.

Docetaxel is known to cause chemotherapy-induced alopecia, with an 83.4% incidence in phase 2 trials; however, it also appears to be related to PCIA.²⁰ A PubMed search of articles indexed for MEDLINE was performed using the terms permanent chemotherapy induced alopecia, chemotherapy, docetaxel, endocrine therapies, hair loss, alopecia, and breast cancer. More than 400 cases of PCIA related to chemotherapy in breast cancer patients have been reported in the literature from a combination of case reports/series, retrospective surveys, and at least one prospective study. Data from some of the more detailed reports (n=52) are summarized in the Table. In the single-center, 3-year prospective study of women given adjuvant taxane-based or non–taxane-based chemotherapy, those who received taxane therapy were more likely to develop PCIA (odds ratio, 8.01).⁹

All 3 of our patients received taxanes. Interestingly, patient 3 underwent 2 rounds of chemotherapy 14 years apart and experienced full regrowth of the hair after the first course of taxane-free chemotherapy but experienced persistent hair loss following docetaxel treatment. Adjuvant endocrine therapies also may contribute to PCIA. A review of the side effects of endocrine therapies revealed an incidence of alopecia that was higher than expected; tamoxifen was the greatest offender. Additionally, using endocrine treatments in combination was found to have a synergistic effect on alopecia.¹⁸ Adjuvant endocrine therapy was used in patients 2 and 3. Although endocrine therapies appear to have a milder effect on hair loss compared to chemotherapy, these medications are continued for a longer duration, potentially contributing to the severity of hair loss and prolonging the time to regrowth.

Furthermore, endocrine therapies used in breast cancer treatment decrease estrogen levels or antagonize estrogen receptors, creating an environment of relative hyperandrogenism that may contribute to FPHL in genetically susceptible women.¹⁸ Although taxanes may cause irreversible hair loss in these patients, the action of endocrine therapies on the remaining hair follicles may affect the typical female pattern seen clinically. Patients 2 and 3 who presented with FPHL received adjuvant endocrine therapies and had positive family history, while patient 1 did not. Of note, patient 3 experienced worsening hair loss following the addition of anastrozole, which suggests a contribution of endocrine therapy to her PCIA. Our limited cases do not allow for evaluation of a worsened outcome with the combination of taxanes and endocrine therapies; however, we suggest further evaluation for a synergistic effect that may be contributing to PCIA.

Conclusion

Permanent alopecia in breast cancer patients appears to be a true potential adverse effect of taxanes and endocrine therapies, and it is important to characterize it appropriately so that its mechanism can be understood and appropriate treatment and counseling can take place. Although it may not influence clinical decision-making, patients should be informed that hair loss with chemotherapy can be permanent. Treatment with scalp cooling can reduce the risk for severe chemotherapy-induced alopecia, but it is unclear if it reduces risk for PCIA.^12,15 Topical or oral minoxidil may be helpful in the treatment of PCIA once it has developed.^7,8,15,22 Better characterization of these cases may elucidate risk factors for developing permanent alopecia, allowing for more appropriate risk stratification, counseling, and treatment.