Improvements in diagnosis and advances in targeted therapies have contributed to the increasing numbers of breast cancer survivors. The most recent estimate by the Surveillance Epidemiology and End Results (SEER) database estimates nearly 2.8 million breast cancer survivors alive as of 2013, an increase from previous estimates.¹ As the numbers of survivors have increased and as many of those survivors are living decades beyond their treatment, issues affecting survivorship and overall quality of life (QOL) have moved to the forefront of breast cancer research. Identification and classification of the persistent and late consequences of breast cancer treatment have become critical endpoints in many newly developed clinical trials. In fact, with the input of patient advocates contemporary clinical trial development frequently includes assessment of outcomes equally according to efficacy and anticipated impact on future QOL.

The NCCN considers an individual a cancer survivor from the time of diagnosis through the balance of her life which results in a heterogeneous spectrum of survivors from diagnosis to immediate posttreatment to permanent survivorship.² In contrast, the timing at which point a woman considers herself a survivor may differ by the stage and treatment factors of her disease. However, the process of psychosocial adaptation begins at the time of diagnosis as women are faced with a variety of treatment choices. A shared decision-making model around treatment and follow-up care has been associated with improved QOL.³ Further, researchers have investigated QOL both within 5 years of diagnosis and beyond 5 years demonstrating that while more than 50% of survivors reported specific treatment-related symptoms they still had excellent physical and emotional well-being and equivalent QOL when compared to healthy age-matched controls.^4–6 Clearly, while women vary widely in their response to diagnosis and treatment most return to rich and rewarding lives after treatment. The growing number of survivorship programs and the recent development of survivorship guidelines by the NCCN is a testament to survivors’ needs and aim to focus on both cancer surveillance and health and well-being issues. These health issues can be classified as persistent, posttreatment symptoms such as fatigue, premature menopause, sexual dysfunction and fertility concerns, or as long-term complications like lymphedema or cognitive dysfunction.

Monitoring for disease recurrence is an integral part of survivorship and can be associated with significant anxiety. Updated ASCO guidelines in 2013 reviewed 14 new publications including 3 meta-analyses and 5 randomized trials published since 2006.⁷ The consensus panel continues to recommend regular follow-up visits with clinical exams every 3 to 6 months for the first 3 years, every 6 to 12 months in years 4 and 5, and annually thereafter. Women should complete mammography 12 months after diagnosis and at least 6 months after the completion of radiation therapy in the setting of breast conservation. Then annual mammography is appropriate unless other clinical concerns exist. Annual breast MRI should be performed in women with BRCA mutations who completed breast-conservation surgery but is otherwise not indicated on a routine basis. Data does not support the routine use of tumor markers, blood tests, or any type of body scans or x-rays to identify recurrent disease in otherwise asymptomatic patients.⁸ Despite these clear recommendations, variations in practice exist across surgeons, medical and radiation oncologists, and primary care providers and likely are influenced by patient preferences as well. In fact recent data suggest significant nonadherence to guidelines for mammography and clinic visits among survivors that increased with time since treatment and were more pronounced in Hispanic and black patients.⁹ Interestingly, however, this nonadherence did not affect overall survival. Finally, ASCO encourages clinicians to develop and provide patients with a treatment summary and outline a survivorship care plan including follow-up, long-term side effects, QOL concerns, and symptoms that should prompt a call to a health care provider. This guideline is critical as women are living longer after the diagnosis of breast cancer and as care is more frequently being returned to the primary care physician.

Cancer-related fatigue without an otherwise systemic cause (like anemia) can be a distressing persistent symptom of breast cancer treatment especially given that it is generally unresponsive to increased rest. While it was originally assumed this fatigue would resolve within months of treatment, studies with longer follow-up now suggest that fatigue may affect 20% of survivors and last months to years posttreatment.¹⁰ According to the National Cancer institute, there is an overall lack of agreement in how fatigue is measured and inadequate understanding of the biology which result in problems in designing and implementing clinical trials to assess fatigue.¹⁰ Acknowledging these challenges, mounting data suggest patients participating in increased postsurgical physical activity have less fatigue, greater functional QOL, and less depression.^11–13 Routine aerobic, strength training, and stretching exercise is encouraged in all patients and should be tailored to their ability. Other intervention strategies may include yoga, massage therapy,¹⁴ exercise classes, cognitive behavioral therapy for insomnia, and even psychostimulants in rare cases.

Of the one in five patients who are premenopausal at breast cancer diagnosis, between 33% and 75% become peri- or postmenopausal after treatment.¹⁵ Toxicity to the ovaries from chemotherapy results in decreased estrogen levels and amenorrhea, which can be permanent. The drop in estrogen may be associated with hot flashes or night sweats, sleep disturbance, libido changes, and symptoms of atrophic vaginitis. Tamoxifen and aromatase inhibitors (AIs) are commonly associated with menopausal symptoms due to their antiestrogen effects. AIs have a stronger association with vaginal dryness and atrophy than tamoxifen alone or in combination.¹⁶ Menopausal symptoms not only have an impact on sexual function, body image, QOL, and psychological health, but also impact adherence to hormonal therapy regimens.^17,18 The decision to treat menopausal symptoms is dependent on symptom severity, disturbance of patient’s life, and also patient preference. A comprehensive menopausal program including pharmacological and psychosocial counseling has been shown to improve symptoms and sexual functioning in survivors.^19,20

Estrogen-progesterone hormone replacement therapy (HRT) in the noncancer population is effective in alleviating menopausal symptoms but carries an increased risk of cardiovascular events. In patients with a history of breast cancer, HRT may stimulate hormone responsive cancer cells and has been associated with an increased risk of recurrence.²¹ Therefore, nonhormonal treatments are recommended for breast cancer patients (Table 83-1). Nonhormonal pharmacologic treatments include selective serotonin reuptake inhibitors (SSRIs), clonidine, gabapentin, and serotonin-norepinephrine reuptake inhibitors (SNRIs). Many women may use herbal therapies such as evening primrose, ginseng, and black cohosh, acupuncture, or soy products. Meta-analyses have not shown increased relief of symptoms with herbal therapies over placebo however.^22,23 Concern exists that phytoestrogens present in soy products and black cohosh may stimulate breast cancer growth or interact with adjuvant hormonal therapy.^24,25 Until further study is completed, survivors should not be advised to use supplements with phytoestrogens. Potential lifestyle changes including weight loss, smoking cessation, keeping the core body temperature cool, and dressing in loose layers may help alleviate some menopausal symptoms.

SSRIs must be used with caution in patients receiving tamoxifen as they reduce the metabolism of tamoxifen into the active metabolite endoxifen by inhibiting the cytochrome P450 enzyme CYP2D6.²⁶ Paroxetine and fluoxetine are the strongest inhibitors of CYP2D6. Venlafaxine is the weakest CYP2D6 inhibitor and thus may be safer in patients taking tamoxifen. The impact of this reduced efficacy of tamoxifen on survival or recurrence is unknown. SSRIs and SNRIs also have known side effects including weight gain and decreased libido. However, the relief of vasomotor symptoms may outweigh these side effects for patients with severe symptoms. If the patient has no change or no relief of her symptoms after a month, it is reasonable to try a different medication. Gabapentin may also decrease hot flashes.^27,28 Evening administration of gabapentin may circumvent the hot flashes that are associated with insomnia and arousal from sleep. Evening dosing may also avoid the side effects of gabapentin seen during the day.

Sexuality after breast cancer is a complex issue. While between 60% and 85% of patients report that cancer has affected their sexual well-being or sexual relationships, over half say they have not spoken to a health care professional regarding their issues.^29–31 It is essential, though challenging, to determine which aspect of sexuality the patient is having difficulty with including arousal, desire, inhibited orgasm, or painful intercourse.

Symptoms of atrophic vaginitis include vaginal dryness, dyspareunia, pruritus, and urinary urgency. Vaginal dryness can lead to painful coital intercourse. It is treated with nonhormonal vaginal lubricants. Water- and silicone-based lubricants are preferred to glycerine-based lubricants which can potentiate yeast infections. Astroglide, KY products, and Liquid Silk are examples of personal lubricants that can be used as needed alone or with longer acting vaginal moisturizers such as Replens. Topical vaginal estrogens remain controversial, and more research is needed on their safety in breast cancer patients. Severe vaginal atrophy may lead to vaginal stenosis. Treatment involves vaginal dilators and lubrication. While lubricants may aid in penetrative intercourse, it should be noted that engagement in sexual intercourse does not always equate to sexual satisfaction.

Arousal and desire are multifactorial. Desire may be affected by the woman’s emotions, hormonal changes, and lifestyle. Anorgasmia may be secondary to psychological distress, medications, other chronic diseases, or lack of desire. Therapy for both anorgasmia and decreased arousal and desire includes counseling, increased foreplay, clitoral stimulation devices, sexual positioning, and normalization of use of sexual aids.

Body image and satisfaction with sexuality change after both mastectomy and partial mastectomy with radiation.³² Women may find it difficult to look at themselves naked, be embarrassed in their partner’s presence, feel lacking in femininity, or hide their body from their partner.^31–33 While breast reconstruction may improve body image after mastectomy in some patients, less than half of women opt for breast reconstruction.³⁴

The quality of a survivor’s support network and partnered relationship consistently affects sexual health after breast cancer.^35,36 Personal relationships face many relational tensions and communication challenges after diagnosis and treatment. The roles of the patient and partner may evolve from lover to caregiver or friend, sexual function may be lost out of anxiety, fear, or shame, and concerns about desirability, femininity, and performance may become pervasive. Patients who feel an emotional separation or perceive fear of intercourse by their partner are more likely to have dissatisfaction with their sex life and engage in sexual activity less frequently.³⁷ Their concerns about their sexual relationships are very similar to the level of concerns of patients in couple’s therapy with up to 10% reporting relationship difficult or breakdown.³⁸ While partner rejection is associated with a negative impact on sexual health, partner acceptance does not always resolve the negative feelings.³¹ Physicians should prepare patients for both menopausal and sexual changes and give them explicit permission to come to them with concerns.

Around 6% of women diagnosed with breast cancer are under the age of 40. Younger or premenopausal survivors report lower QOL, greater severity of depressive symptoms, and higher levels of stress compared to older survivors.^39,40 Often younger women have not begun or completed their childbearing at the time of diagnosis. As a consequence, fertility preservation becomes a primary concern for younger breast cancer patients. Infertility caused by cancer treatment is a source of significant psychosocial distress and decreased QOL.^39–41

The American Society of Clinical Oncology (ASCO) recommends health care providers refer patients within their reproductive years for fertility counseling.⁴¹ While the proportion of patients who do not remember any discussion regarding fertility has been gradually decreasing over time, up to 50% of patients still have no memory of a conversation about fertility at time of treatment planning.^42–47

Issues surrounding the timing of fertility counseling are complex. Some fertility planning techniques such as embryo or oocyte cryopreservation require 2 weeks from the beginning of a menstrual cycle. If a patient chooses this option, cancer treatment may be delayed a month or more. Additionally, a patient may require some time to contemplate her fertility options before making a decision. Conversely, additional psychological stress may be added unnecessarily if a patient has a premature referral to reproductive counseling in a case where chemotherapy is not indicated. Specialized counseling regarding fertility has been associated with both an increased QOL and less regret, regardless of whether action is taken to preserve fertility.^48,49 Counseling should include descriptions of the available techniques, success and failure rates, complications, and whether a procedure is experimental or not.

Although up to 45% of women express a desire for a future child at the time of diagnosis, only 3% to 8% go on to have a full-term pregnancy after cancer treatment.^39,47,50,51 Ovarian reserve, or the capacity of the ovary to provide eggs capable of fertilization, decreases naturally as women age. Despite some women experiencing resolution of their treatment-associated amenorrhea, patients should be counseled that their reproductive potential may be impaired even in the presence of regular menses.^52,53

The choices for fertility preservation vary depending on the patient’s age, planned cancer treatment, partner status, ovarian reserve, time frame available, and the possibility the cancer has metastasized to the ovaries.⁵² The main options for fertility preservation include embryo cryopreservation, oocyte cryopreservation, and temporary ovarian suppression (Table 83-2). Cryopreservation of ovarian tissue or of immature oocytes is still experimental. The data regarding efficacy of temporary ovarian suppression with luteinizing hormone-releasing hormone analogue (LHRHa) is conflicting.^54–59 Both oocyte and embryo cryopreservation require 10 to 14 days of ovarian stimulation and are expensive. They may be offered when it is reasonable to delay treatment by 2 to 6 weeks and the patient is below the age of 38 to 40 with the possibility to recover an adequate number of oocytes.⁵² Concern remains regarding the impact of the ovarian stimulation required for embryo or oocyte cryopreservation upon hormone-sensitive tumors. Further research in this area is required.