Sexual quality of life in hormonotherapy for breast cancer patients

Breast cancer is one of the most common malignant neoplasms affecting women worldwide. In Brazil, there is an estimated risk of 61.61 new cases per 100,000 women for each year of the triennium 2020-2022.1 Those carcinomas that express hormone receptors are candidates for antiestrogen therapy, and this population corresponds to 71.3% of Brazilian patients with breast carcinoma.2 3 The use of hormone therapy (HT) for these patients has benefits described since the 1970s as adjuvant treatment or for metastatic disease (remissive or palliative).4 5 6 7 8 9

The most commonly used classes involve selective estrogen receptor modulators (SERM, the most common representative of which is Tamoxifen) and aromatase inhibitors (AI, such as anastrozole, letrozole, and exemestane). HT causes many side effects that, by blocking the antiestrogenic action, reproduce the physiological postmenopausal hypoestrogenism. This can have a great impact on all dimensions of the quality of life of these women. In Brazil, there are review articles on the subject, but, at least in our literature searches, there are few clinical studies directed mainly to the sexual health.10 11 12 13 14 15 16

This paper aims to evaluate and try to quantify impacts of HT on sexual activity and quality of life in patients with breast carcinoma, according to age, pre- and post-menopausal hormonal status, and type of hormone therapy used (Tamoxifen or Anastrozole).

The study was approved by the Research Ethics Committee of the Faculdade de Ciências da Saúde da Pontifícia Universidade Católica de São Paulo (PUC-SP), in Sorocaba (SP), Brazil. This is a transverse observational study and the evaluation instruments were applied to patients with breast cancer who consented to participate after signing the Free and Informed Consent Form (Appendix I). All of them were on hormonal treatment with Tamoxifen (T) or Anastrozole (A) at the time of the interview, either in adjuvant mode or advanced disease, in the pre-or postmenopausal state, at the outpatient level, in the Clinical Oncology Service of the Conjunto Hospitalar de Sorocaba (Seconci-SP), convened with the PUCSP School of Medicine. Patients with psychological disorders that would not allow them to understand the questionnaires and illiterate patients were excluded from the analysis.

The used instruments were: FACT-B (Functional Assesment of Cancer Therapy) (indicated for quality of life assessment for patients with breast carcinoma)17 and the FSDS-R (Female Sexual Distress Scale Revised) in Portuguese.18 Questions are presented in 5 Likert mode responses. For the FSDS-R the score level equal to or greater than 11 discriminates women with sexual dysfunction; this index was not used in the evaluations, observing only the descriptive answers. (Appendix II).

Both questionnaires were already validated to Portuguese: FACT-B at a study by LATORRE, Maria do Rosário Dias de Oliveira from Universidade de São Paulo - USP at 2012 and FSDS-R at a study by LIMA, Sonia Maria Rolim Rosa from Faculdade de Ciências Médicas Santa Casa de São Paulo at 2010.

For the making of contingency tables, the absolute numbers for the categories “Almost always or always” + “Most of the time” + “Sometimes” (“Favorable” group) versus “Few times” + “Almost never or never” (“Unfavorable” group) were grouped. The same was done for FACT-B, with the grouping “Not at all” + “A little” versus “More or less” + “A lot” + “Very much”. Women who used (by crossover) both medications were included in the group with Anastrozole, because at the time of the evaluation all of them were on Anastrozole therapy.

The questions were given to the patient (Appendix II) and answered without any external assistance. None were required to answer all the questions – we aimed to provide participants privacy and no interference with the questionnaires. Therefore, some calculations present with smaller numbers because of the participants' lack of response to some questions.

Other parameters evaluated were age, time of menopause, marital status, and current sexual activity. The initial clinical stage, the current status of HT (adjuvant or remissive), and the time and type of previous treatment were collected from the patients' medical records and from questions asked by the researchers.

Descriptive data were presented as absolute and relative numbers, and means; 2 × 2 contingency tables with chi-square by Fisher's exact test, and Yates' correction in the classical requirements, with the statistical significance level for p<0.05.

Forty-one women, with a mean age of 55.4 years (from 35 to 77 years) were evaluated in the year 2019. The menopausal women had a mean menopausal period of 10.92 years (from 2 to 28 years). 38 stated living maritally and/or being sexually active, and 3 did not respond. Mean time on hormone therapy was 36.84 months. For all those who had a crossover, its order was from Tamoxifen to Anastrozole, but the factors requiring the treatment changes or discontinuation were not documented. Table 1 shows the parameters of the study population.

Except for one patient (premenopausal), all responded that they understood the need for their hormone treatment, and none of them have suspended their treatment. If they could suspend it, 4/8 of premenopausal women and 4/26 of those in menopause said they would, which results in 8/34 women (23.52%). The main reason was because of side effects (7/40; 17.5%), and three patients pointed out specific situations: 2 for living too far from the treatment facilities and 1 for the need to change daily life schedule.

A cross-referencing of numbers in contingency tables determined no statistical correlation when considering the pre-and postmenopausal groups for the following conditions: impact of adverse effect vs. discontinuation of medication; impact on their life vs. impact of adverse effect; impact of adverse effect vs. discontinuation or change of medication.

The analyses regarding the FSDS-R instrument (Table 2) showed statistically significant numbers (p< 0.05) when comparing the groups with Tamoxifen (T) versus Anastrozole (A) in the following questions: question M. “In the past 4 weeks, how satisfied were you with your ability to achieve orgasm (“enjoy”) during sexual activity or intercourse?”, favoring the T group; questions Q and R regarding dyspareunia (pain at initial and after penetration, respectively) also favored the T group; question P, regarding overall sexual satisfaction, favored the group receiving tamoxifen, as well, wich coincids with question GS7 of the FACT-B Instrument additionally favoring the T group (see Table 3). For the other questions regarding orgasm, the comparisons between the T and A groups did not prove to be significant (questions K and L). The questions regarding sexual desire, activity and frequency of intercourse, sexual arousal and vaginal wetness found no diferences between groups A and T, as well.

Quality of life was assessed by the FACT-B instrument, and Table 3 summarizes these data for the questions that achieved statistical significance. No significance was found for any question in the GP (physical well-being), emotional well-being (EG), functional well-being (FG) groups, all questions in the Social/family well-being (GS), and additional worries (B) groups. The only exception was for one question referring to satisfaction with sex life (GS) and feeling sexually attractive (B), both favoring the Tamoxifen group.

A direct question about the impact of hormone treatment on their quality of life showed thar 4/8 of premenopausal and 4/24 menopausal women reported a decrease in it after starting hormone therapy, exactly 8/34 women, or 23.52%.

The main side effects of HT for patients with breast cancer are already known, being coincident with the physiological postmenopausal hypoestrogenism. An observation study of up to 2 years of adjuvant treatment with aromatase inhibitors showed a significant rate of sexual dysfunction - 93% using the Female Sexual Function Index, with 75% of the women concerned about their sexual health. In the group that had maintained sexual activity, 79% developed new sexual problems in these 2 years.19

Tamoxifen was the gold standard for treating hormone-sensitive breast cancer in postmenopausal women, but the development of aromatase inhibitors, with its' mechanism of action more appropriate for postmenopausal women, made them the first choice for this group. With its increasing use among postmenopausal women, new toxicities such as arthralgias, bone loss, and cognitive dysfunction were described. Interestingly, these effects are poorly represented in older quality of life assessment instruments.20 21 22 Other options of treatment to the group of high-risk HR-positive/ HER2 negative patients includes: ovarian suppression or ablation in premenopausal patients, leading to a menopausal state; and most recently, it has been shown efficacy in the combination of endocrine therapy with 2 years of adjuvant Abemaciclib (an CDK4/6 inhibitor). But this last treatment was not represented in our study since none of our patients had access to this medication.

Most papers in the literature focus on postmenopausal patients and more systemic complications with apparent less interest in genital and sexual aspects23 24 25 26 which reflects in daily clinical practice. The Female Sexual Distress Scale- Revised (FSDS-R) is one of the assessments instruments created to assess the stress associated with female sexual dysfunction,27 but there is no standard to these assessments and, not surprisingly, this may be due to the complexity regarding the study of sexual dysfunctions.16 28 This makes medical practice and research on the subject quite challenging.

A study evaluated 83 patients 3 years after the diagnosis of breast cancer and concluded that 77% presented sexual dysfunction.10 A longitudinal evaluation evaluating more than 760 patients with a medium interval of 6.3 years detected that while the physical and emotional functionalities progressively improved during HT, the complaints of reduced sexual activity, reduction of vaginal lubrication and urinary incontinence remained significant.29 We have found other non-Brazilian studies that also reported similar results regarding general and sexual quality of life, also pointing that sexual quality of life remains as one of the most affected life domains among postmenopausal breast cancer patients undergoing HT.30 31 32 33 34 An Iranian study also noted the unmet need for assessment of the impact on the quality of life in this group of women.31 Three Brazilian literature reviews have also outlined these aspects, but mainly focusing on the general quality of life.13 14 15 In our results, the observation of the number of women in the anastrozole group – and therefore mainly postmenopausal and more elderly women, who did not answer the question about orgasm (question M), may suggest that these menopausal women may feel embarrassed or uncomfortable about this issue in their sexual lives.

The ATAC study (anastrozole and tamoxifen alone or in cross-over, for adjuvant therapy)35 evaluated, in two studies, quality of life (including FACT-B) and some sexual aspects.36 No significant impacts on quality of life were observed, but the study did observe worsening vaginal dryness, dyspareunia and reduced libido in the groups with Anastrozole. This matches with our study observations.

Between 20 to 40% of patients on HT will present sexual complaints28, and more specifically, 30% to 40% of patients under Tamoxifen37 and more than 50% among those on aromatase inhibitors29. In the study conducted by Baumgart et al, women on Tamoxifen or Anastrozole were compared with women not on hormone therapy: 73.9% of patients on Anastrozole reported reduced vaginal lubrication, versus 40% of those on Tamoxifen; dyspareunia was reported in 56.5% of those in Anastrozole group versus 31.3% in the Tamoxifen group; 42.4% of patients reported dissatisfaction with their sex lives on Anastrozole versus 18% on Tamoxifen.37 Our conclusions coincide with this and suggests Tamoxifen as a drug with less impact on these common sexual dysfunctions, providing a better quality of sexual life when compared to Anastrozole.

A Brazilian study assessed quality of life in 58 breast cancer women undergoing HT either on tamoxifen or anastrozole. Findings suggest quality of life was not different between these two groups, but interestingly, only 44% of the women were completely adherent to treatment in that study.38

Regarding adherence to hormone treatment, the CANTO cohort, published in 2018, studied self-reported adherence to Tamoxifen in women on adjuvant HT for breast cancer and prospectively assessed serum tamoxifen concentration. 87.7% of the patients reported maintaining Tamoxifen, and 12.3% admitted stopping treatment, discontinuing, or switching to an aromatase inhibitor.39

The fact that Tamoxifen was used in premenopausal women may account for the maintenance of orgasmic capacity, less dyspareunia, and the reported feeling of being sexually attractive seem in T group. On the other hand, in the A group, the side effects on sexual health were significant both in adjuvant and remissive modality. In spite of all this we could question: aren't we being condescending to such impactful adverse events when prescribing HT?40

The intimacy related to sexual health presents a challenge for these evaluations. A published thesis suggests a method to approach sexuality with patients undergoing HT, beginning with permission from the patient to start a discussion and gradually evolving until specific complaints and proper therapy.41 Our observation, as mentioned early, found that a significant number of women in the postmenopausal group undergoing HT in the A group did not answer questions regarding orgasm (question M from FSDS-R). This points to the need for better methods for approaching sexual health-related discussions with HT patients, which should consider not only organic issues such as vaginal dryness but also psychic aspects such as depression, self-image, and counseling.42 43 44 45 46 47 48

Our study had limitations such as small number of patients (41 in total); bigger amostrage in Tamoxifen group (46,35%); the majority of patients were postmenopausal (68%) which could enhance the impact on sexual life as we have seen in some studies cited above; and almost 20% of patients were at a stage IV or recurrent disease, which could lead to a bigger impact not only in sexual quality but also in general quality of life, leading to misunderstanding results.

Hormonal treatment for breast cancer in women has an important impact on quality of life in general physical, social, family, and emotional well-being, leading to a reduced overall quality of life and sometimes to discontinuation of treatment (CANTO STUDY CITED ABOVE). But beyond those, there is also a significant impact is observed specifically on sexual health, which might be more present at younger patients and be different between the two class of drugs most widely used (SERMS vs. aromatase inhibitors).

Since these effects on sexual health does not seem life threatening or be more discrete than systemic or acute ones (such as thrombosis, osteoporosis etc) or even be more difficult to access with the patients in normal daily practice, maybe physicians are not paying the attention that it needs and sexual quality of life is being neglected.

And even the patient might neglect it, maybe because of the stigma and fear of breast cancer and its possible recurrence, or even underestimating the impact these issues bring to daily life.

Our study suggested a major impact in general sexual well-being and orgasmic capacity in the A group; and although we had a 100% adherence rate, more than 20% of patients admitted that they would abandon treatment if they could. We had few patients who had a crossover, all of them from Tamoxifen to Anastrozole, the reasons were not documented, but maybe they have had undesirable side effects and tried another drug because of that.

Unfortunately, the number of Brazilian observations is scarce, and among those few, the majority relayed data from foreign populations. Hence, we believe our work can bring novel and reliable data to support clinical decisions during hormonal therapy for breast cancer patients in Brazil and abroad.