Women, whose sexual capacity is compromised by a breast cancer diagnosis, are not only coping with concerns about their own health and survival but are also worried about their partner’s QOL and overall well-being. Indeed, partners of women with cancer are dramatically affected by loss of sexuality and intimacy. Hawkins et al. demonstrated that cessation or decreased frequency of sex and intimacy was reported in 79 % of male partners of women affected by breast cancer. Renegotiation of sexuality and intimacy after cancer was reported by only 14 % of these partners. These alterations to sexuality were associated with feelings of self-blame, reflection, sadness, anger, and lack of sexual fulfillment [23]. Further, male partners of women diagnosed with breast cancer often express several conflicting emotional states including feeling worried about their significant other’s health, having the desire to engage in sexual activity, and feeling guilty about wanting to increase sexual intimacy. These feelings, in turn, can lead to resentment and withdrawal from their partner and overall relationship discord [24]. Evidence suggests partners of breast cancer patients greatly benefit from increased social support even years after an apparent cure [25]. Specifically male partners who take on a new role as caregiver in the relationship experience difficulties with emotional changes, challenges to their masculinity, and new stressors [26]. These new roles and feelings also contribute to changes in sexuality and intimacy in relationships, making support for partners all the more necessary.

Whether or not hormonal adjuvant therapy will be a primary treatment in breast cancer in a given case depends on histological subtype, stage of disease, and patient characteristics. Approximately 60–75 % of all breast cancers are estrogen/progesterone hormone receptor positive (ER+, PR+) [27]. For the ER+/PR+ histological variants of breast cancer, endocrine therapies are well established for both early-stage and advanced disease with regimens varying by menopausal status at diagnosis, with reduced risk of recurrence and improvement in survival achieved with long-term therapy [28].

Tamoxifen is a selective estrogen receptor modulator (SERM) which acts as an estrogen antagonist in breast tissue (a benefit), but as an estrogen agonist in the endometrium and other tissues (conferring potential for harm). Tamoxifen is used as an adjuvant treatment in managing premenopausal breast cancer in the setting of ER+/PR+ tumors [29]. Its estrogen receptor agonist activity in some tissues yields several associated risks. These risks include an increased rate of ovarian cysts observed, as high as 20 % in premenopausal patients, an increased rate of abnormal uterine bleeding and endometrial cancer (a 2.7 fold risk while on therapy), as well as a small but significant increase in rates of uterine sarcoma [30–32]. In addition to these concerns, several studies have observed sexual complaints associated with tamoxifen use. A cross-sectional study observed dyspareunia in 54 % of patients regardless of patient age, surgical treatment of the primary cancer, or chemotherapy [33, 34]. This finding is supported by several other studies noting a high rate of gynecological and sexual complaints in patients on tamoxifen [35]. A longitudinal study of breast cancer patients placed on tamoxifen after chemotherapy observed frequent dyspareunia (47 %) and low sexual interest (44 %) in these patients regardless of chemotherapy regimen, with a high correlation between gynecological complaints and decreased sexual interest (p < 0.0005) [34]. However, several studies have assessed hormonal treatment in the context of other therapies and have found the strongest correlation of sexual side effects to chemotherapy with weak or absent correlation between tamoxifen and sexual symptoms [36–38]. A prospective study in postmenopausal breast cancer patients on tamoxifen assessed sexual function after 6 months of therapy in comparison to pretreatment baseline measures. This study revealed a significant increase in gynecological symptoms (p < 0.0001); however there was no increase in the percentage of women who reported sexual dysfunction (30 % at both baseline and after 6 months of treatment) [39].

Raloxifene is another SERM which has demonstrated a decreased risk of breast cancer recurrence in receptor-positive disease and is also approved for the treatment of postmenopausal osteoporosis [40, 41]. Raloxifene and tamoxifen were directly compared in a two-arm, randomized, double-blinded clinical trial of 19,747 women for over 5 years of treatment. This study found increased efficacy of tamoxifen in prevention of recurrence of invasive breast cancer, with risk ratio of 1.24 for raloxifene/tamoxifen (CI, 1.05–1.41.2), with significantly lower rates of endometrial cancer, uterine hyperplasia, and thromboembolism observed in the raloxifene arm and no significant differences in mortality between the two arms [42]. Patient symptom analyses from the same trial indicated that sexual function was slightly better for participants assigned to tamoxifen (age-adjusted repeated measure odds ratio, 1.22 %; CI, 1.01–1.46) however greater mean symptom severity for gynecological problems (p < .001) and vasomotor symptoms (p < .001) as compared to the raloxifene group [43]. There is otherwise limited data on raloxifene’s impact on sexual function in breast cancer patients, and studies of raloxifene in osteoporosis therapy have not demonstrated significant changes in sexual function with this agent [44–46].

Aromatase inhibitors (AIs) are almost exclusively used as an adjuvant strategy in postmenopausal patients with hormone-responsive (ER+/PR+) tumors. By inhibiting the enzyme aromatase, AIs prevent tissue-level conversion of endogenous androgens to estrogens and have been shown to improve patient survival in this population [47]. Side effects of these therapies often include significant vasomotor symptoms, as well as vulvovaginal atrophy (VVA), vaginal dryness, and dyspareunia. A population-based study comparing sexual symptoms in patients taking AIs for breast cancer therapy with age- and menopausal status-matched controls demonstrated decreased sexual interest in 50 % of AI patients, sexual dissatisfaction in 42.4 % of patients, and inadequate vaginal lubrication in 72 % of patients. All of these rates were significantly more common (p < 0.05) than in matched controls [48]. A prospective study of tamoxifen versus AI use found significantly greater genitourinary symptoms of menopause in AI users compared with tamoxifen. These symptoms were consistent with the strong estrogen suppression achieved with AI [22].

For premenopausal breast cancer patients with hormone-responsive cancer (ER+/PR+), ovarian suppression, either through use of GnRH agonists or with bilateral oophorectomy, may be used to optimize results and minimize recurrence risk [29]. In general, premenopausal women who experience abrupt surgical or chemical menopause often experience immediate and severe vasomotor symptoms that contribute to QOL deterioration in this vulnerable population. An increasing number of premenopausal women with breast cancer may face treatment with ovarian suppression, given recently published data from the Suppression of Ovarian Function (SOFT) trial suggesting a survival benefit in a subset of premenopausal women when ovarian suppression was used in combination with aromatase inhibition [49]. Additionally, many pre- and postmenopausal women are now being advised to extend adjuvant hormonal therapy beyond the previously established 5-year course based on a small but statistically significant long-term survival benefit with 10 years of tamoxifen use compared to 5 years [50]. An increased duration of tamoxifen exposure has been associated with a higher prevalence of vaginal atrophy [51], with higher rates of sexual dysfunction to be expected in those patients.

Hormonal therapy (HT) has long been recognized as the most effective therapy for management of hypoestrogenic symptoms of menopause, including vasomotor symptoms and symptoms of vaginal atrophy. Efficacy relates to dose of estrogen component of HT formulations, as well as route of therapy (vaginal route of estrogen being most effective against focal vaginal symptoms) [54]. While the past decade has witnessed an evolution in our perspective on the place of HT in the menopause management for the healthy aging female population, little has changed as regards our understanding of safety or additive risk of HT use in breast cancer survivors.

The role of HT in breast cancer patients remains contentious, and data in this regard are sparse and predominantly observational. In a systematic review of eleven observational trials, Col et al. determined that there was no quantitative increase in recurrence risk among breast cancer patients using HT. This review compared 214 breast cancer survivors on heterogeneous systemic HT regimens for a mean of 22 months compared to 623 patients without HT therapy. The women on HT were on average 52 months post initial breast cancer diagnosis at the time of HT initiation. Controlling for disease stage, heterogeneity of initial trial design, and distance from date of diagnosis, a relative recurrence risk of 0.64 (CI 0.36–1.15) was observed in patients who had received HT [55]. An absence of increased risk of breast cancer recurrence has been replicated by a number of other case control and observational trials over the last two decades [56–59]. While these studies have all been methodologically limited by their retrospective design, there have been two major prospective clinical trials examining HT in breast cancer survivors, one of which did demonstrate a significant increase in breast cancer recurrence. The Stockholm study (n = 378) and Hormone Replacement After Breast Cancer Therapy – Is It Safe? (HABITS) (n = 438) trials were both conducted in Sweden in the late 1990s. The HABITS trial was an open trial of breast cancer patients randomized to either 2 years of hormone replacement (estrogen only or continuous combined estrogen-progesterone) or to best-alternative options for menopausal symptoms (although specific non-HT therapies were not detailed). The study was designed to demonstrate non-inferiority between arms, and the primary end point was any new breast cancer event with a planned follow-up of 5 years. The trial was halted early in 2003, at mean follow-up of 2.1 years, due to a significant increase of recurrent breast cancer in the HT arm with a hazard ratio of 3.5 (95 % CI = 1.5–7.4) [60]. At 4 years reevaluation after closure of the HABITS trials, the increased risk of cancer recurrence remained significant with a cumulative recurrence rate of 22.2 % in the HT arm and 8.0 % in the control arm (HR = 2.4, 95 % CI = 1.3–4.2). However, no differences in cancer mortality were observed between study arms [61]. The Stockholm study ran concurrently with, and was structurally similar to, the HABITS trial except for its use of lower progesterone exposure through cycled sequential progesterone dosing. The Stockholm study was halted after a median follow-up of 4.1 years because of the findings of the HABITS trial. Upon cessation of the trial, there were no significant differences in breast cancer recurrence between HT and non-HT arms, with a hazard ratio of 0.82 (95 % CI = 0.35–1.9) [62]. Analysis of Stockholm Study participants at 10 years follow-up showed no increased risk of breast cancer recurrence in the HT arm as compared to the non-HT arm, with cumulative recurrence rates of 32 % in the HT group and 25 % in the non-HT group (HR = 1.3; 95 % CI = 0.9–1.9). There was also no difference in mortality between the Stockholm study arms at 10 years follow-up [63]. Notably, there were some limitations to these studies. HT regimens were not standardized in either trial, and some patients were taking both tamoxifen and HT simultaneously, which is not a standard practice in the United States [64]. Nonetheless, based on existing data, the official position of the American College of Obstetricians and Gynecologists is that patients with a history of hormone-sensitive breast cancers should not use HT as a first-line therapy for hypoestrogenic symptoms. Current ACOG guidelines further state that breast cancer survivors choosing to initiate HT to improve QOL should be counseled about the potential for breast cancer recurrence with hormonal therapy [65].

Concerns over the risks associated with HT have recently led to the development of newer third-generation SERMs for symptom management with the goal of limiting risk. Ospemifene (trade name Osphena) is reported both preclinically and clinically to have antagonistic or neutral effects on breast, with agonist activity on bone and vaginal tissue [66, 67]. It is currently available as an oral preparation, FDA approved for the treatment of moderate dyspareunia caused by VVA, and with ongoing research into its effects on bone density. There is currently no data on its use in breast cancer survivors, and it is not currently indicated for these patients as long-term data is not available, nor is data on this population available. Clinical trials in the postmenopausal population have demonstrated improvement in genitourinary menopausal symptoms and improvements in histologic signs of vaginal atrophy [68]. There is a low rate of reported systemic side effects, with the most common complaint of facial flushing with use [68, 69]. Although its estrogen antagonistic effect on the breast tissue makes it an appealing symptomatic therapy for study in breast cancer patient, safety and efficacy of this agent in cancer survivors are yet to be established [70].

Tibolone, while not a SERM, is a synthetic steroid with activity on estrogen and progesterone receptors and mainly acts as an agonist at estrogen receptors [71]. It is prescribed outside the United States for osteoporosis and is being investigated as treatment for female sexual dysfunction [72]. Efficacy on vasomotor symptoms has been positive thus far. However, one group recently examined tibolone in the setting of breast cancer patients in a prospective randomized controlled trial and reported an increased risk of breast cancer recurrences in women receiving tibolone for HT [73]. A separate case-control study confirmed tibolone’s safety for endometrial cancer survivors, another hormone-sensitive cancer, with no adverse effects on disease-free or overall survival [74]. However, tibolone has not received approval for use in breast cancer survivors for any indication in the United States or Europe.

For postmenopausal women with symptoms of atrophic vaginitis, topical estrogen therapy can be very helpful [75]. Many formulations are available including creams, tablets, and rings, and a recent Cochrane review has indicated that all formulations have proven more beneficial than placebo or nonhormonal lubricants for control of symptomatic VVA [76]. While many symptomatic breast cancer survivors may be interested in low-dose topical estrogen therapies, there remains however a theoretical concern with their use, particularly by those with hormone receptor-positive cancers given the potential for systemic absorption and the slight increases in circulating estrogen concentrations reported among some vaginal estrogen users [77, 78]. This issue of systemic absorption was evaluated in few trials; in one such trial, systemic absorption was limited to a short interval after initiation of vaginal estrogen therapy, yet the magnitude of systemic absorption was significantly reduced as the trophic effects of estrogen on vaginal epithelium developed few weeks later [77]. In another trial, non-hysterectomized postmenopausal women receiving commonly used doses of vaginal estrogens demonstrated no increased risk of endometrial proliferation or hyperplasia suggesting minimal absorption [78]. As to the risk of recurrent breast cancer among vaginal estrogen users, data remains quite limited and the quality of evidence is low. Le Ray and colleagues performed a case-control study with 13,479 adult women with a previous diagnosis of breast cancer demonstrating no increase in the risk of recurrence in tamoxifen-treated patients using local hormonal therapy over the course of 3.5 years of follow-up [79]. Vaginal estrogen type, duration of therapy, and dosage were not assessed. Rates of recurrence in those patients using vaginal estrogen therapy while undergoing aromatase inhibitor therapy versus patients on aromatase inhibitors alone have not been directly compared [80]. Notably, although available evidence has been reassuring, safety concerns often limit patient use of topical hormonal therapies. Some trials show rates as low as 3 % of hormone receptor-positive breast cancer patients using this treatment modality [79, 81].

Pelvic floor physical therapy is well studied and utilized frequently for urinary incontinence and pelvic organ prolapse; however it is understudied in areas of sexual dysfunction [84–86]. Evidence continues to emerge as to the efficacy of physical therapy programs not only for urinary and defecatory disorders but also for sexual dysfunction. The physical therapist may employ educational sessions, cognitive behavioral therapy, vaginal dilator therapy, pelvic floor muscle strengthening, and relaxation techniques with biofeedback, stretching, and massage. A recent review article by Rosenbaum highlighted the idea that there are promising studies in this area [87]. While there is limited data, biofeedback in particular has undergone controlled studies for treatment of sexual dysfunction specifically in the setting of vulvar pain syndromes [87]. A recent small phase I/II trial assessed the efficacy and tolerability of pelvic floor physical therapy combined with protocolled vaginal lubrication in 25 breast cancer patients with complaints of dyspareunia over 4 weeks with follow-up extending through 26 weeks. Patients reported significant improvements in dyspareunia, sexual function, and quality of life over the course of the study, with maximum benefit achieved by 12 weeks and no reported adverse events [88]. Although research in pelvic floor physical therapy and dilator use continues to develop, the absence of serious side effects and the benefits observed to date indicate that they may be a helpful addition in a multidisciplinary approach to treatment of pelvic floor dysfunction in breast cancer patients.