Abstract
Background/Aim: Chemotherapy-induced alopecia (CIA) is a significant concern for patients with breast cancer (BC). Although scalp-cooling therapy has shown efficacy in reducing scalp hair loss, its effects on eyebrow and eyelash preservation have been unclear.
Patients and Methods: We conducted a prospective observational study of 154 patients with BC who received perioperative chemotherapy from 2016 to 2024. Seventeen of these patients underwent scalp cooling using the Paxman Scalp Cooling System (Paxman, Houston, TX, USA). Patient-reported outcomes were assessed via questionnaires evaluating the degree of hair loss at the scalp, eyebrows, eyelashes, and body hair.
Results: Scalp cooling significantly reduced the incidence of severe hair loss (score 4-5) at the scalp (p<0.001). Although the differences in eyebrow and eyelash hair loss were not significant (p=0.095 and p=0.199, respectively), a trend toward reduced severe alopecia was observed. No protective effect was observed for body hair (p=0.446).
Conclusion: Scalp-cooling therapy is effective for preventing severe scalp hair loss and may offer partial protection against eyebrow and eyelash alopecia. These findings support its broader application in BC care to enhance patients’ quality of life.
Introduction
Chemotherapy is an essential component of perioperative treatment for early-stage breast cancer, significantly reducing this cancer’s recurrence and mortality rates (1). Perioperative chemotherapy used in the perioperative period to treat breast cancer is necessary to achieve a curative outcome, but it is often associated with distressing adverse effects. Chemotherapy-induced alopecia (CIA) is a common adverse effect of chemotherapy and one of the most distressing (2-7). Although CIA has been known to be a transient condition, alopecia may affect not only the scalp but also the eyebrows, eyelashes, and pubic hair (2, 3, 7). This may negatively affect patients’ body image, sexuality, and self-image and cause psychological distress, making it more difficult for the patients to continue undergoing chemotherapy (2, 3, 7-10). Patients often report that eyebrow and eyelash loss contributes more significantly to their sense of facial identity than scalp hair loss, making these areas critical for psychological wellbeing. A study of Japanese patients revealed that 60% of the physical symptoms ranked as most distressing by the patients were related to appearance, including eyebrow and eyelash loss (9).
A prospective observational study by our research group found that CIA occurred in 100% of the study’s patients who had sequential anthracycline and taxane regimens, with severe hair loss (≥75%) reported in all cases (7). Importantly, this hair loss was not confined to the scalp; it extended to the eyebrows (82.4%), eyelashes (77.9%), and body hair (92.6%). The recovery of eyebrow, eyelash, and body hair was significantly delayed in the postmenopausal patients, highlighting the impacts of age and hormonal status on the course of CIA.
Scalp-cooling therapy has emerged as the only evidence-based method for preventing CIA (11-14). Despite the increasing acceptance of scalp-cooling therapy in clinical practice, its effects have been studied almost solely in terms of scalp-hair preservation. There remains a lack of data regarding the potential impact of scalp-cooling therapy on eyebrow and eyelash hair loss, which are as distressing as scalp hair loss but less understood. We conducted the present study to evaluate the effectiveness of scalp cooling for preventing CIA at various anatomical sites, including the eyebrows and eyelashes.
Patients and Methods
This single-center prospective observational study included 154 patients with primary breast cancer who underwent perioperative chemotherapy at Gunma University (Maebashi, Japan) between January 2016 and May 2024. Among them, 17 patients received scalp-cooling therapy with the Paxman scalp-cooling system (Paxman Corp., Houston, TX, USA). The remaining 137 served as the control group. The oncologic management for all of the patients included breast surgery with the appropriate axillary lymph node procedures (including the lymph node sentinel procedure and lymph node dissection), radiotherapy, chemotherapy, hormonal therapy according to the patient’s age and the tumor’s hormonal status, and a trastuzumab+pertuzumab regimen for human epidermal growth factor receptor 2 (HER2)-positive breast cancer.
All of the patients received a standard anthracycline- and taxane-based chemotherapy regimen [e.g., FEC (5-fluorouracil, epirubicin, and cyclophosphamide) or AC (adriamycin and cyclophosphamide) followed by docetaxel or paclitaxel] or TC (docetaxel+cyclophosphamide), and the HER2-positive patients received additional trastuzumab± pertuzumab therapy. The chemotherapy protocols were as follows. The FEC regimen was a combination of epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2, and 5-fluorouracil 500 mg/m2 for four cycles every three weeks. The AC regimen was a combination of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 2-3 weeks for a total of four cycles and docetaxel 75 mg/m2 every three weeks for four cycles or weekly paclitaxel 80 mg/m2 for 12 cycles. The TC regimen was a combination of docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 for four cycles every three weeks.
Scalp cooling using the Paxman system was administered to patients who requested it; it was started 30 min before the chemotherapy infusion and continued during the infusion and for 90 min after the infusion. The Paxman cap maintained the wearer’s scalp temperature at approx. 19°C circulating a coolant throughout the cap.
A self-reported and validated questionnaire assessed the severity of alopecia at four anatomical sites: the scalp, eyebrows, eyelashes, and body hair (pubic, leg, and axillary hair). The degrees of alopecia were as follows Five points: 100% hair loss, four points: ~75%, three points: ~50%, 2 points: ~25%, and 1 point: ~0%. Severe alopecia was defined as a score of 4 or 5 points (75%-100% hair loss). The patient-reported outcomes were collected at the time of their chemotherapy completion. The following clinical data were also obtained: the patient’s age, tumor TNM stage, estrogen receptor (ER) expression status, progesterone receptor (PgR) expression status, and the HER2 score of the primary tumor. The ER and PgR statuses were assessed by using the Allred score ≥3 points, which indicates ER and PgR positivity (15, 16).
HER2 over-expression was determined using an immunohistochemistry (IHC) analysis and a fluorescence in-situ hybridization (FISH) analysis with IHC 3+ or IHC 2+/FISH+ indicating HER2 positivity (15). Breast cancer subtypes were defined based on the patient’s ER, PgR, and HER2 status as luminal-type breast cancer (ER-positive, HER2-negative), luminal-HER2 type (ER-positive and HER2-positive), HER2 type (ER-negative and HER2-negative), and triple-negative (ER-negative and HER2-negative) breast cancer (15). A univariate statistical analysis was conducted using Fisher’s exact test or the χ2-test with Yates’ correction. For the comparisons of pairs of groups, Student’s t-test was used. Differences were considered significant when the p-value was <0.05.
Ethical approval. All procedures performed in studies involving human participants were in accordance with the ethical standards of the Clinical Ethics Committee of Gunma University and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.
Results
Among the 154 female Japanese patients with breast cancer who received perioperative chemotherapy during the study period, 17 were treated with scalp cooling and 137 did not undergo scalp cooling, as detailed in Table I. The median age in the scalp-cooling group was 50 years (range=24-63 years), and that in the non-cooling (control) group was 51 years (range=29-76 years). There was a slight difference in the clinical stage between the scalp-cooling and control groups but no significant difference in age, breast cancer subtype, or chemotherapy regimen.
Patient background.
Regarding the prevalence of CIA, hair loss occurred at the scalp but also the eyebrows, eyelashes, and body hair (pubic, lower limbs, axillary) in most of the patients (Table II). In the control group, severe scalp alopecia was present in almost all of the 137 patients (98.5%). Eyebrow alopecia was present in 110 patients of the control group (80.3%), and 47 (34.3%) had severe eyebrow alopecia. Eyelash alopecia was present in 106 patients of the control group (77.4%), with 28 (20.4%) reporting severe eyelash alopecia. Body hair alopecia (pubic, leg, and axillary hair) was described by 127 control patients (92.7%), and 72 (52.6%) had severe body hair alopecia.
Prevalence and degree of chemotherapy-induced alopecia (CIA).
The scalp-cooling therapy significantly reduced the incidence of severe alopecia at the scalp (p<0.001). In the scalp-cooling group, severe scalp alopecia was observed in 10 of the 17 patients (58.8%). Eyebrow alopecia was present in 15 (88.2%), and two patients (11.8%) had severe eyebrow alopecia. Eyelash alopecia was present in 14 patients (82.4%), with a single patient (5.9%) having severe eyelash alopecia. Body hair alopecia was described by 17 patients (100%), and seven (41.2%) had severe body hair alopecia. Although the differences in eyebrow and eyelash hair loss between the scalp-cooling and control groups were not significant (p=0.095 and p=0.199, respectively), a clear trend toward reduced severe alopecia was observed in the scalp-cooling group. No significant between-group difference was observed for body hair loss (p=0.446).
Discussion
Patients with BC are likely to be aware of treatment-related changes in their appearance, and the cosmetic aspect is often very important (7, 8). Such changes in appearance, especially hair loss, can be considered an important element of patients’ distress (8, 17-19), and CIA is one of the most distressing adverse effects of chemotherapy (2-7). CIA generally manifests initially as patterned hair loss that is most prominent on the scalp (2), but CIA hair loss also occurs in the eyebrows, eyelashes, and other body sites (2, 3, 7). The prevalence and degree of CIA differ among all of these sites. It is important for clinicians to fully understand that CIA can be a psychological burden for patients, concerning not only the scalp but also the eyebrows and eyelashes.
Hair loss results from disturbances of the normal hair-shaft production and hair-follicle cycling (2, 20). The degree of hair loss may depend on the percentage of hairs that are in the anagen phase. The scalp is the area that is most frequently affected by CIA, because up to 90% of scalp hairs are normally in the anagen phase (3). The timing of the hair loss that occurs in the eyebrows, eyelashes, and body is thus suspected to represent the rate of hair in the anagen phase.
Scalp cooling was proposed as a preventive therapy for alopecia relatively recently (11-14). Scalp-cooling therapy is thought to exert its protective effect against CIA through two primary mechanisms: (i) vasoconstriction that reduces blood flow to hair follicles and thus reduces the local concentration of cytotoxic drugs, and (ii) a suppression of the metabolic activity of hair matrix keratinocytes, rendering them less susceptible to chemotherapy-induced damage. Our present findings revealed that scalp CIA in early-stage breast cancer patients undergoing standard chemotherapy can be prevented by scalp cooling. The observed reduction in scalp hair loss supports these mechanisms. Interestingly, we also observed a trend toward reduced eyebrow and eyelash alopecia. Although these areas are not directly cooled by the Paxman scalp-cooling system, it is plausible that secondary cooling via conduction or shared vascular territories might provide partial protection. The eyebrows and eyelashes are anatomically proximal to the scalp and may benefit from regional cooling effects.
Our finding that the patients’ body hair (pubic, lower limb, axillary) was not affected by the scalp-cooling treatment may also support this possible mechanism. This result is clinically meaningful. Eyebrow and eyelash alopecia are often noted by patients as particularly distressing because of their important role in facial expression and identity. Our observation that eyebrow and eyelash alopecia tended to decrease with scalp cooling–although this improvement was initially unintended – suggests that the scalp-cooling mechanism may be useful in the prevention of CIA at these non-scalp sites as well, and that future alopecia prevention strategies could also consider the prevention of eyebrow and eyelash alopecia.
Study limitations. The number of cases was relatively small. However, the data were based on self-report questionnaires, so although there may have been sampling bias, there was no investigator bias at the time of sampling. In addition, the study results were derived from patients’ reports of subjective outcomes and not from objective findings by the investigators. However, patients’ survey responses may reflect the true problems they are experiencing. To our knowledge, the present investigation is the first prospective observational study to examine the effect of scalp cooling on eyebrow and eyelash hair loss. Although our results did not reach statistical significance (probably due to the small sample size), they suggest a potential benefit that merits further study. Additional investigations of larger numbers of cases worldwide are needed.
In conclusion, scalp cooling significantly reduced severe chemotherapy-induced scalp alopecia and may offer partial protection against eyebrow and eyelash hair loss. Given the psychosocial burden associated with chemotherapy-induced alopecia (including at non-scalp regions), these findings support the broader use of scalp-cooling therapy and warrant further investigations into adjunctive measures for facial hair preservation.
Acknowledgements
The Authors thank the Gunma University School of Nursing for their cooperation.
Footnotes
Authors’ Contributions
TF analyzed data and wrote the initial draft of the manuscript. KI, MA, KT, MO, and SO collected data and were involved in the initial study conception and design. TF, KI, MA, KT, MO, SO and HT were involved in drafting and revising the manuscript. All Authors have read and approved the final manuscript.
Conflicts of Interest
The Authors have no conflicts of interest to declare in relation to this study.
Funding
No funding was received.
Artificial Intelligence (AI) Disclosure
During the preparation of this manuscript, a large language model (DeepL) was used solely for language editing and stylistic improvements in select paragraphs. No sections involving the generation, analysis, or interpretation of research data were produced by generative AI. All scientific content was created and verified by the authors. Furthermore, no figures were generated or modified using generative AI or machine learning-based image enhancement tools.
- Received August 15, 2025.
- Revision received September 9, 2025.
- Accepted September 10, 2025.
- Copyright © 2025 The Author(s). Published by the International Institute of Anticancer Research.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
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