Efficacy of low-dose oral minoxidil in the management of anticancer therapy-induced alopecia in patients with breast cancer: A retrospective cohort study.

To the Editor: Alopecia is feared by most patients undergoing systemic anticancer therapy for breast cancer because of its negative impact on quality of life.1Lemieux J. Maunsell E. Provencher L. Chemotherapy-induced alopecia and effects on quality of life among women with breast cancer: a literature review.Psychooncology. 2008; 17: 317-328Crossref PubMed Scopus (235) Google Scholar Currently, evidence regarding management of persistent chemotherapy-induced alopecia (pCIA) and endocrine therapy-induced alopecia (EIA) in patients with breast cancer is lacking.2Freites-Martinez A. Shapiro J. van den Hurk C. et al.Hair disorders in cancer survivors.J Am Acad Dermatol. 2019; 80: 1199-1213Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 3Bhoyrul B. Asfour L. Lutz G. et al.Clinicopathologic characteristics and response to treatment of persistent chemotherapy-induced alopecia in breast cancer survivors.JAMA Dermatol. 2021; 157: 1335-1342Crossref PubMed Scopus (8) Google Scholar, 4Freites-Martinez A. Chan D. Sibaud V. et al.Assessment of quality of life and treatment outcomes of patients with persistent postchemotherapy alopecia.JAMA Dermatol. 2019; 155: 724-728Crossref PubMed Scopus (38) Google Scholar Although previous studies demonstrated successful use of low-dose oral minoxidil (LDOM) in pCIA, EIA was not included, and responses were assessed only by evaluating clinical photographs.2Freites-Martinez A. Shapiro J. van den Hurk C. et al.Hair disorders in cancer survivors.J Am Acad Dermatol. 2019; 80: 1199-1213Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar,3Bhoyrul B. Asfour L. Lutz G. et al.Clinicopathologic characteristics and response to treatment of persistent chemotherapy-induced alopecia in breast cancer survivors.JAMA Dermatol. 2021; 157: 1335-1342Crossref PubMed Scopus (8) Google Scholar Therefore, using quantitative measurements, we assessed the efficacy of LDOM in patients with breast cancer diagnosed with pCIA and/or EIA. We retrospectively reviewed medical records, standardized clinical photographs, and trichoscopic images (Folliscope5.0, LeadM) to assess the alopecia pattern, severity, treatment response, and post-treatment changes in vertex hair density and thickness. Alopecia severity was evaluated using the Common Terminology Criteria for Adverse Events, version 5.0.2Freites-Martinez A. Shapiro J. van den Hurk C. et al.Hair disorders in cancer survivors.J Am Acad Dermatol. 2019; 80: 1199-1213Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar For patients who received both chemotherapy and endocrine therapy, EIA was diagnosed when there was complete hair regrowth prior to alopecia aggravation postinitiation of endocrine therapy. Combined pCIA and EIA was defined as incomplete hair regrowth 6 months after chemotherapy completion with alopecia aggravation postinitiation of endocrine therapy. Overall, 100 female patients with breast cancer diagnosed with pCIA and/or EIA at a single dermatology clinic from January 2013 through June 2022 were included. Patients with pCIA were more likely to present with diffuse alopecia (P < .001; Table I) and, although not statistically significant, more severe alopecia than patients with EIA alone (P = .058). Trichoscopic evaluation at the cross-point of a line connecting the external auditory canals and the midsagittal plane revealed significantly lower baseline vertex hair caliber in patients with combined pCIA and EIA than in patients with EIA alone (P = .002).Table IDemographics and clinical characteristics of patients with breast cancer diagnosed with anticancer therapy-induced alopecia (n = 100)Demographics and clinicalcharacteristicspCIA aloneEIA aloneCombined pCIA + EIAP value∗Bold P values indicate statistical significance (P < .05). P values were calculated using one-way analysis of variance and Fisher’s exact test.Number of patients, n206911Age, mean (SD) Breast cancer diagnosis46.2 (9.0)46.4 (9.8)48.6 (7.9).753 Alopecia diagnosis50.8 (9.8)49.9 (9.6)52.5 (7.4).702Offending agents, n (%) Taxane19 (95.0)N/A11 (100.0) 5-fluorouracil, doxorubicin, cyclophosphamide1 (5.0)0 (0.0) SERMN/A47 (68.1)7 (63.6) Aromatase inhibitors22 (31.9)4 (36.4)Alopecia pattern, n (%) Diffuse alopecia8 (40.0)2 (2.9)6 (54.5)<.001 Androgenetic alopecia-like pattern12 (60.0)67 (97.1)5 (45.5)Time from chemotherapy completion to alopecia diagnosis, month, median (range)39.0 (13.3-139.5)N/A25.3 (14.5-151.0)Time from endocrine therapy initiation to alopecia diagnosis, month, median (range)N/A25.2 (1.0-136.0)22.5 (7.5-150.0)Baseline alopecia severity, n (%)‡Among those with standardized clinical and trichoscopic photos available at baseline (n = 95).n = 19n = 65n = 11 Grade 114 (73.7)59 (90.8)8 (72.7).058 Grade 25 (26.3)6 (9.2)3 (27.3)Baseline hair parameters, mean (SD)‡Among those with standardized clinical and trichoscopic photos available at baseline (n = 95).n = 19n = 65n = 11 Hair density/cm2154.2 (26.2)159.0 (27.6)150.3 (33.4).583 Hair thickness, μm60.7 (13.4)68.0 (12.4)53.3 (6.9).001†Statistically significant differences found between the endocrine therapy-induced alopecia alone group and the combined persistent chemotherapy-induced alopecia + endocrine therapy-induced alopecia group using Tukey’s Honestly Significant Difference test (P = .002, 95% CI = [4.85, 24.56]).EIA, Endocrine therapy-induced alopecia; n, the number of patients; pCIA, persistent chemotherapy-induced alopecia; SERM, selective estrogen receptor modulator.∗ Bold P values indicate statistical significance (P < .05). P values were calculated using one-way analysis of variance and Fisher’s exact test.† Statistically significant differences found between the endocrine therapy-induced alopecia alone group and the combined persistent chemotherapy-induced alopecia + endocrine therapy-induced alopecia group using Tukey’s Honestly Significant Difference test (P = .002, 95% CI = [4.85, 24.56]).‡ Among those with standardized clinical and trichoscopic photos available at baseline (n = 95). Open table in a new tab EIA, Endocrine therapy-induced alopecia; n, the number of patients; pCIA, persistent chemotherapy-induced alopecia; SERM, selective estrogen receptor modulator. Treatment outcomes were evaluated in 56 patients treated with minoxidil who had standardized clinical and trichoscopic photos available at baseline and last follow-up. All patients were scheduled for a routine 3-month interval follow-up. Concomitant treatment with 1.25 to 5.0 mg daily LDOM and once daily 5% topical minoxidil solution (n = 37, 66%) demonstrated better treatment responses (P = .002; Table II) and a higher percentage increase in hair density/cm2 from baseline (P = .003) compared to topical minoxidil monotherapy (n = 19, 34%). Post-treatment changes in hair thickness (μm) did not differ significantly between the 2 groups (P = .540). Only 1 patient required LDOM withdrawal due to periorbital edema.Table IIComparison of treatment response and post-treatment changes in hair growth parameters between the treatment groups (n = 56)Main resultsTopical minoxidil monotherapy (n = 19)LDOM + Topical minoxidil (n = 37)‡Once daily low-dose oral minoxidil: 20 patients with 1.25 mg, 12 patients with 2.5 mg, and 5 patients with 5.0 mg.P value∗Bold P values are statistically significant (P < .05). P values were calculated using the independent t test and Fisher’s exact test.BaselineLast follow-upBaselineLast follow-upAlopecia severity, n (%) Grade 116 (84.2)15 (78.9)30 (81.1)35 (94.6) Grade 23 (15.8)4 (21.1)7 (18.9)2 (5.4)Treatment response, n (%) Complete response§Improvement of alopecia severity from grade 2 to grade 1.0 (0.0)5 (13.5).002 Partial response‖Improvement of scalp coverage with no change in alopecia grade.10 (52.6)29 (78.4) Stable disease¶No definite change in scalp coverage.7 (36.9)3 (8.1) Progression of disease#Worsening of alopecia.2 (10.5)0 (0.0)Hair density/cm2, mean (SD)162.4 (24.2)168.5 (24.2)†Statistically significant differences found between hair parameters before and after treatment using the paired samples t test (Topical, P = .016; Low-dose oral minoxidil + Topical, P < .001).152.7 (28.2)170.8 (27.6)†Statistically significant differences found between hair parameters before and after treatment using the paired samples t test (Topical, P = .016; Low-dose oral minoxidil + Topical, P < .001).Hair thickness, μm, mean (SD)66.7 (13.1)67.4 (12.6)60.6 (11.8)59.9 (10.2)Post-treatment changes in hairparameters, mean (SD) Hair density increase, %3.9 (6.4)13.2 (15.7).003 Hair thickness increase, %2.1 (13.3)−0.04 (11.8).540Duration of treatment, month, mean (SD)17.7 (18.0)20.3 (17.9).610Adverse events, n (%) Hypertrichosis0 (0.0)5 (13.5) Edema0 (0.0)2 (5.4) Palpitation1 (5.0)1 (2.7) Headache and dizziness0 (0.0)1 (2.7)LDOM, Low-dose oral minoxidil; n, the number of patients.∗ Bold P values are statistically significant (P < .05). P values were calculated using the independent t test and Fisher’s exact test.† Statistically significant differences found between hair parameters before and after treatment using the paired samples t test (Topical, P = .016; Low-dose oral minoxidil + Topical, P < .001).‡ Once daily low-dose oral minoxidil: 20 patients with 1.25 mg, 12 patients with 2.5 mg, and 5 patients with 5.0 mg.§ Improvement of alopecia severity from grade 2 to grade 1.‖ Improvement of scalp coverage with no change in alopecia grade.¶ No definite change in scalp coverage.# Worsening of alopecia. Open table in a new tab LDOM, Low-dose oral minoxidil; n, the number of patients. The retrospective study design, small sample size, and variations in treatment duration are limitations. A previous study comparing 1 mg daily LDOM and once daily 5% topical minoxidil over 24 weeks documented nonsignificant differences in hair density increase in female-pattern baldness.5Ramos P.M. Sinclair R.D. Kasprzak M. Miot H.A. Minoxidil 1 mg oral versus minoxidil 5% topical solution for the treatment of female-pattern hair loss: a randomized clinical trial.J Am Acad Dermatol. 2020; 82: 252-253Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar The higher LDOM doses (1.25-5.0 mg) and concomitant use of topical minoxidil for pCIA and/or EIA could have produced the significant differences observed in our study. Although larger, more controlled studies are needed, this suggests that the effects of topical minoxidil in pCIA and/or EIA could be reinforced with concomitant LDOM. In conclusion, combined use of LDOM and topical minoxidil showed more promising treatment results than topical minoxidil monotherapy and was well-tolerated in our cohort of patients with anticancer therapy-induced alopecia (Supplementary Fig 1, available via Mendeley at https://doi.org/10.17632/xjp7c5mc8h.3). None disclosed.