Sexual quality of life in young women with breast cancer during adjuvant endocrine therapy: objective assessment and patient-reported supportive measures.

Purpose: sexual quality of life (QoL) is affected during and after breast cancer (BC) treatment. Young women are more frequently and severely affected. We analyzed the sexual and global QoL in less than 51 years old women with BC receiving adjuvant endocrine therapy for at least 2 years, to analyze sexual dysfunction after the acute treatment phase. We also questioned women on the actions taken individually and on those they would nd useful to address these issues. Methods: a prospective study was conducted to evaluate the sexual QoL of young women with BC during the adjuvant endocrine treatment and to assess patient-reported supportive measures. Results: a total of 45 women completed the 3 EORTC questionnaires and an additional specic questionnaire proposed in the context of the study. We showed a deterioration of the sexual QoL and a poor communication with healthcare professionals about this issue. Most patients (88.9%) declared important that sexuality should be discussed with caregivers and that the partner should be involved in the discussion. The majority of patients (60%) had taken at least one action to overcome the sexual problems, in order of frequency: local treatment like vaginal moisturizer, consultation with a psychologist, while a consultation with a sexologist remained rare. Most of these interventions (63%) originated from the patient herself. Most supportive methods used by the were at highlighting for a professional counseling on Finally, patients suggested supportive measures they would nd useful and appropriate to develop in clinic.


Introduction
Advances in breast cancer (BC) diagnosis and treatment have led to the improvement of the patients' prognosis with a 5-year survival in wealthier countries reaching now 90% [1]. Disease and its treatment can affect day-to-day life of BC survivors and these physical, psychological and social concerns became important issues to be addressed in clinic [2]. Among these quality of life (QoL) concerns, sexual di culties have been more recently studied [3][4][5][6][7]. In this regard, a speci c health-related quality of life questionnaire (HRQLQ) dedicated to evaluate sexual dysfunction related to the disease and its treatment, in cancer patients, the EORTC SHQ-22, has recently been developed [8].
We previously published the results of a longitudinal assessment analyzing the sexual and global QoL of 106 women with hormone receptor-positive (HR+) BC, during the rst year of endocrine therapy, using the EORTC SHQ-22 and global HRQLQ [9]. This study showed a deterioration of patient's sexual QoL as compared to women in the general population and a very low communication level about sexual themes between patients and healthcare givers.
In this study, we focused on young patients, less than 51 years old, a population whose QoL and sexuality is more frequently and severely affected following BC care [9][10][11][12][13]. We analyzed the sexual and global QoL in these women with HR+ BC during endocrine therapy for at least 2 years, to analyze sexual dysfunction after the acute surgical, chemotherapeutic and radiotherapeutic treatment phase. We also used an additional speci c questionnaire, proposed in the context of our study, to question women on the actions taken individually to address sexual issues and on which supportive measures they would nd useful and appropriate to develop in clinic.

Study design and subject recruitment
This unicentric prospective study (CUPIDON 2) was conducted in the Institut du Cancer de Montpellier (ICM). The protocol was approved by the French Ethics Committee and the internal review board of the institution. Patients received an information letter and all provided written consent before the enrolment.
The primary objective was to evaluate the sexual QoL of women younger than 51 years old, with HR + BC during endocrine therapy received for at least two years, using the EORTC SHQ-22 questionnaire. The secondary objectives were to evaluate the non-sexual QoL at the same time-point using the EORTC QLQ-C30 [14] and QLQ-BR23 [15] questionnaires; to evaluate the information received by patients about sexual issues; to evaluate the need for speci c management of sexual troubles and to describe supportive measures or therapeutic interventions used by women on their own initiative using the speci c Cupidon questionnaire, proposed for the study. Eligible women were between 18 and 51 years old, sexually active, displaying HR + early BC, having completed surgery as well as chemotherapy and/or radiotherapy when indicated. They all had received their endocrine therapy for at least 24 months.

Data And Measures
General health and socio-demographic information, including employment status, physical activity and partner status were self-reported by participants. Age, weight, size, menopausal status, pathology report, type of treatment (type of surgery, radiotherapy, chemotherapy) as well as co-morbidities were collected from the medical records.
Patients were invited to complete the three EORTC HRQLQ only once.
The general EORTC QLQ-C30 questionnaire dedicated to all cancer patients includes 30 items assessing the global health status with 5 functional scores (physical, role, cognitive, social and emotional) and 9 symptom scores (nausea and vomiting, pain, fatigue, dyspnea, sleeping disturbances, appetite loss, constipation, diarrhea and nancial di culties).
The speci c EORTC QLQ-BR23 module dedicated to breast cancer patients includes 23 items allowing to assess 4 functional scores (body image, sexual functioning, sexual enjoyment, future perspective) and 4 symptom scores (systemic side effects, arm symptoms, breast symptoms, being upset by the hair loss).
The EORTC SHQ-22 is a multidimensional QoL instrument used to measure sexual health in patients with cancer (men or women). This new tool covers both sexual functioning and psychosexual components. It includes 8 items on sexual satisfaction, 3 items on sexual pain and 11 single items, in an integrative approach, leading to 7 functional scales and 4 symptom scales.
In these questionnaires, higher scores in the functioning scales indicate better functional level whereas higher scores in the symptom scales indicate rather severity of problems. A user agreement for the use of the EORTC SHQ-22 was signed.
In addition, a home-made questionnaire containing 11 questions was proposed to patients in order to explore (1) the information regarding sexuality received during treatment, (2) the supportive measures or therapeutic interventions used by patients to overcome sexual dysfunction, (3) the need and acceptability for speci c management of sexual dysfunction. This speci c Cupidon questionnaire is reproduced in extenso in the supplemental data.

Statistical Considerations
In this descriptive study, the sample size was based on the recruitment capacity of our institution, which represented a potential of around 50 patients meeting the inclusion criteria of the study for the planned duration. Considering an 80% acceptance rate (20% of refusal), a total of 40 patients were expected to participate. The inclusion of at least 40 patients permits to estimate (for descriptive purposes) the mean scores of the dimensions of the EORTC SHQ-22 (ranged from 0 to 100) and its 95% con dence intervals (95% CI) with a width of 15, and hypothesizing a standard deviation of 24 [16].
Scorings of the three EORTC HRQLQ were calculated according to the EORTC Scoring Manuals and results were presented as means and standard deviations (SD). Categorical variables were described using frequencies and percentages.
Statistical analysis was performed using the Stata v16 software (College Station, TX, 2019).

Patients' Characteristics
Among the 65 patients contacted between February and April 2020 to participate in the study, 11 were not eligible (8 had no sexual activity, 2 had relapsed, 1 had discontinued her endocrine therapy) and 9 refused to participate. A total of 45 patients have been included and completed the four questionnaires. Clinical and socio-demographic characteristics are summarized in Table 1. Median age was 45 years. A majority of women had been treated by breast conserving surgery (62%), and had received chemotherapy (87%).
Most women (87%) had received endocrine treatment for 2 to 5 years. Sixty % of women were premenopausal at cancer diagnosis. Endocrine therapy consisted mostly of tamoxifen (73%), and included a chemical castration in 18% of cases. According to the body mass index (BMI), 33% and 11% of patients were overweight and obese, respectively. Most patients (58%) practiced regular physical activity, i.e. minimum 30 minutes, 3 times a week, and 76 % were professionally active. All women were sexually active at baseline (inclusion criteria) and 17 % declared a previous history of sexual problem either in the couple (5%) or of their partner (12%).  Table 2. The importance attributed to the sexual activity appeared relatively preserved (mean score of 60.00) but sexual satisfaction was lower (mean score of 45.80). The libido and the impact of treatment on sexual life scores were low (mean scores of 29.63 and 37.78) and the communication about sexuality with professionals score was extremely low (mean score of 11.11). The feeling of security with the partner and the femininity were less altered (mean scores of 52.71 and 59.69 respectively).

Speci c Cupidon Questionnaire
The answers to the speci c Cupidon questionnaire are shown in Table 5 and Table 6.

Discussion
This study described the sexual health and global QoL of 45 women less than 51 years old during adjuvant endocrine treatment for HR + early BC, as well as the actions taken and suggested by these women to overcome the encountered problems.
First of all, women displayed a high level of interest in the study as demonstrated by the 83% participation rate and a high rate of response to the items of the questionnaires.
The scores observed for the sexual QoL evaluation with the EORTC SHQ-22 were similar to those previously observed using the same questionnaire in a population, without age restriction [9], during endocrine therapy (sexual satisfaction scores were 43.43 and 45.80 in the previous and in the current study respectively), with, though, a higher importance for sexual activity in this younger population (scores of 42.95 and 60.00 respectively). The observed score deteriorations were similar, in both studies, with an extremely low score for communication with professionals, and a high level of alteration of the sexual satisfaction and of the libido scores. This deleterious effect of BC and its treatment is consistent to what has been shown in the literature with other questionnaires [17][18][19][20][21] and is signi cant when compared to the French general population in which the rate of sexual satisfaction of women was 88% in a 2006 survey including 6824 women [22]. It should be noted that the professional activity, physical activity and body mass index rates of our study population were similar to those of the same age general population [23,24].
The global QoL deterioration analyzed with the QLQ-C30 and BR23 was also similar to what we previously reported [9] with the most frequent symptoms being fatigue and insomnia.
We explored the actions taken and proposed by patients to overcome these sexual dysfunctions using a home-made questionnaire speci c to our study. Firstly, most patients had not received any information neither, a fortiori, help from their oncologist or caregiver. A vast majority of them declared important that sexuality should be discussed and that their partner should be involved. However, among the women who had received information by their oncologist or any caregiver, the vast majority were satis ed by the received information, which is altogether encouraging, since these caregivers were not trained before the study.
The majority of patients used interventions to overcome sexual problems from their own initiative, underlying the need for a speci c management of this issue. They stated, mostly not based on their personal experience, that it would be desirable to develop, by order of frequency: consultation with a caregiver trained in sexology, vaginal moisturizer, pelvic oor physical therapy, consultation including their partner, consultation with a sexologist, and less frequently, any kind of psychotherapy.
Most patients declared that sexuality remains a minor issue compared to cancer treatment as the main reason to explain why they didn't discuss about it with their oncologist or caregiver. This seemingly contradictory response might re ect the patients' ambivalence about the theme and/or the fact that they want to prioritize the time with their oncologist to focus on the medical information regarding the cancer and its treatment. The role of the oncologist is probably mostly to raise the subject with the patient and to question for the need for such a dedicated consultation.
The limitations of our study are the low number of patients included and the absence of longitudinal evaluation. The strengths are the homogeneity of this young women population as well as the use of standardized EORTC questionnaires integrating physical, psychological and social aspects to evaluate sexual QoL. Moreover, despite the fact that the speci c Cupidon questionnaire is not a validated research instrument, asking women their opinion on the actions that could be useful and appropriate to develop in clinic is crucial. This latter information from the involved women going through this issue is precious and should be used to identify the actions to be taken to support these women. The key proposals from the affected patients should be considered to tailor patient's management, the nal goal being to improve the QoL of our patient with the adequate intervention and support.