Novel Study of Endocrine Therapy-Induced Hair Loss

Pam Harrison

April 17, 2018

It's not only chemotherapy that causes breast cancer patients to lose their hair. Treatment with endocrine therapy (ie, tamoxifen or an aromatase inhibitor) can also cause hair loss and have a negative impact on quality of life, even when the loss is only mild in severity, a novel study suggests.

On the other hand, treatment with topical minoxidil (Rogaine, Johnson & Johnson) can restore hair growth, so the loss is potentially treatable, the investigators add.

"There are tens of thousands of breast cancer survivors on endocrine therapies, and the remarkable improvements in patient survival that have been achieved through their care have led to patients now being concerned about quality of life issues, like partial hair loss," senior author Mario Lacouture, MD, Memorial Sloan Kettering Cancer Center (MSKCC), New York City, told Medscape Medical News in an email.

The study is the first to characterize endocrine therapy–induced alopecia (EIA) in patients with breast cancer. EIA has been anecdotally reported but never systematically described. The study was published online April 11 in JAMA Dermatology.

The investigators retrospectively identified a cohort of 112 female patients seen at MSKCC, all of whom had EIA.

"Those who either previously received cytotoxic chemotherapy or had a previous diagnosis of alopecia or any scalp condition were excluded from the study," the investigators note.

Standardized clinical photographs of the scalp were taken from several angles with the hair parted and combed in the center. Responses to a questionnaire concerning hair were collected in order to assess the effect that alopecia had on patients' quality of life. At baseline, the prevailing trichoscopic feature was the presence of vellus hairs as well as intermediate- and thick-density terminal hair shafts, the researchers report.

Patients were treated with topical minoxidil 5%. The effects of treatment were measured by a single investigator at 3 and 6 months.

The researchers note that vellus hairs may be present as a result of unsynchronized miniaturization of hair follicles, one of the hallmarks of so-called androgenetic alopecia. As Lacouture explained, androgenetic alopecia is a pattern of hair loss similar to that which occurs in men and women with age. It is characterized by a thinning of hair on the temples, a receding hairline, and loss of hair at the top of the head.

In the current study, evaluation of the standardized clinical photographs, available for 93% of the group, showed that there was a more prominent recession of hair in the frontotemporal area in 76% of patients than in the midanterior hairline, the investigators note.

"Also, the specific type of alopecia seen in 86 patients (83%) was mild to moderate alopecia on the crown area of the scalp," they add.

Moreover, 92% of patients developed grade 1 alopecia; only 8% of the group developed grade 2 alopecia. Alopecia severity was graded using the Common Terminology Criteria for Adverse Events scale.

Data on alopecia-related quality of life were available for slightly fewer than half of the group (46%). For those patients, the mean score on the hair questionnaire was 25.6.

This score includes measures of emotions, functioning, symptoms, stigmatization, and self-confidence. The highest negative score on the hair questionnaire was in the emotional domain (P < .001).

Grade 1 alopecia represents hair loss of less than 50% that does not require camouflage.

Patients appeared to be negatively affected by even grade 1 hair loss, suggesting, Lacouture indicated, that "not only complete hair loss as seen with chemotherapy is affecting women but also hair thinning or partial hair loss will result in a negative psychosocial impact."

Minoxidil Response

The investigators were able to assess response to topical minoxidil 5% in 41% of the group. Topical minoxidil 2% and 5% is the only agent approved by the US Food and Drug Administration for the treatment of androgenetic alopecia in women.

The investigators determined that 80% of patients who were treated with topical minoxidil experienced either moderate to significant improvement in alopecia.

The researchers explain that both estrogens and androgens are important modulators of hair growth.

"When endocrine receptor activation and pathway signaling are blocked, dihydrotestosterone levels increase, and this action may contribute to the induction of alopecia in susceptible women receiving ET [endocrine therapy]," they observe.

This mechanism of action suggests that alopecia induced by endocrine therapy may be "physiologically similar" to androgenetic alopecia; as such, the investigators hypothesize that women with EIA may benefit from other potential treatments for androgenetic alopecia, such as spironolactone (multiple brands).

"Alopecia is often cited as one of the most negative effects on quality of life in patients with cancer, and it has been reported that 8% of patients with cancer would rescind lifesaving therapy had they known they were going to have alopecia," the study authors state.

"Therefore, it should be important for oncology health care professionals treating patients with breast cancer to consider the distress that grade 1 alopecia may have on patients' QoL [quality of life]," they add, especially given the long duration of treatment required with endocrine therapy.

Lacouture added that no randomized studies have investigated whether topical minoxidil should be given prophylactically to women about to receive endocrine therapy, so they cannot recommend that physicians treat women to prevent hair loss.

"However, they should refer women to a dermatologist or initiate minoxidil at the first sign or symptom of hair thinning, until we have better treatments," Lacouture recommended.

Higher Incidence

In an accompanying editorial, Ralph Trueb, MD, Center for Dermatology and Hair Diseases, Zurich, Switzerland, suggests that the reported incidence of EIA may be significantly higher than the oft-cited 4.4%; it may affect as many as one quarter of patients treated with tamoxifen and approximately one third of women who are treated with an aromatase inhibitor. "Not unexpectedly, this would correspond to the estimated prevalence of androgenetic alopecia in the general population of women," Trueb told Medscape Medical News in an email.

Trueb says that female androgenetic alopecia differs from male androgenetic alopecia in that it has a more complex etiology. "Topical minoxidil is as yet the single agent with proven effectiveness for treatment of female androgenetic alopecia," Trueb points out.

"Because its mode of action does not affect estrogen metabolism, it is safe for use in women with hormone-sensitive tumors, as well as for long-term use in women with alopecia at risk for hormone-sensitive tumors," he indicates.

Importantly, however, Trueb also notes that alopecia caused by endocrine therapy may eventually be irreversible if left untreated for a long time.

Early treatment of endocrine therapy–induced hair loss is mandatory. Dr Ralph Trueb

"Therefore, early treatment of endocrine therapy–induced hair loss is mandatory," he said. Alternatively, physicians should prescribe minoxidil prophylactically in women with a history of androgenetic alopecia who are about to undergo endocrine therapy.

"Once hormonal treatment is stopped, there is a chance for preserved hair to remain, even after tapering of minoxidil," Trueb said.

"Therefore, minoxidil treatment should be continued for the total duration of endocrine therapy," he added. "Once the hair is lost, it will not regrow, even after cessation of endocrine therapy," Trueb emphasized.

Chemotherapy-induced hair loss is different from endocrine therapy–induced hair loss; the only way to prevent chemotherapy-induced hair loss — at least to some extent — is through the use of scalp cooling during treatment, he also pointed out.

The study was supported in part by grants from the National Institutes of Health/National Cancer Institute Cancer Center and by Beca Excelencia. Dr Lacouture has received research funding from Berg and Bristol-Myers Squibb and has served as a consultant to Quintiles, AstraZeneca, Legacy, Foamix, Adgero Bio Pharmaceuticals, Janssen Research & Development, and Novocure. Dr Trueb has disclosed no relevant financial relationships.

JAMA Dermatol. Published online April 11, 2018. Full text, Editorial

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