Table 1.

Side effects and recommendations for their management

Side effect	Characteristics	Attitude/recommendation
Lymphedema	10–30% of patients who have undergone axillary node removal and 3–10% of patients treated with selective sentinel node biopsy [10] In recent years, the strategy of substituting axillary lymphadenectomy for axillary radiation is being assessed, without losing effectiveness and with a decreased risk of lymphedema [12]	Preventive measures (hygiene, hydratation, avoiding weights, and wounds) Rehabilitation In some cases, lymphedema surgery may be considered
Ovarian failure and menopause-related symptoms
Repercussions of ovarian function	20 and 80% of women may present amenorrhea secondary to chemotherapy, which may be permanent. The risk depends on the schedule administered and patient’s age at the time of chemotherapy administration	Offer fertility-preserving methods Refer to Reproduction Services prior to systemic treatment administration [13] Do not recommend conception until 3–6 months after completing systemic treatment [13, 14] If the patient is receiving tamoxifen and wishes to become pregnant, hormone therapy must be discontinued between 3 and 6 months prior to allowing conception [13, 15]
Sexual activity	Decrease in libido or vaginal dryness are attributable to both the ovarian failure young women undergo after chemotherapy or hormone therapy and the side effects themselves of hormone therapy (gonadotropin analogues, SERM, aromatase inhibitors) The change in body image and local pain secondary to surgery can also cause dysfunction of sexual activity	Psychological support Use of vaginal lubricants The use of vaginal tablets or hormone creams is controversial
Hot flashes secondary to menopause	They are the result of induced menopause and are aggravated by hormone treatments Both tamoxifen and aromatase inhibitors (anastrozole, letrozole, exemestane) can cause or aggravate hot flashes	If severe, treatment with velafaxine or gabapentin can be used Acupuncture has demonstrated efficacy
Risk of endometrial disease	Women who receive tamoxifen for a long period have a higher risk of suffering endometrial cancer, although these neoplasms are general diagnosed very early have a good prognosis	In patients receiving tamoxifen, annual gynecological examinations are recommended. Postmenopausal women should be evaluated preferably by a gynecologist if they present vaginal bleeding
Bone health	Spontaneous or induced menopause (secondary to chemotherapy, gonadotropin analogues, or oophorectomy) involves decreased bone mineral density This effect can be relevant in young women with early menopause Hormone treatment, especially aromatase inhibitors in postmenopausal women produce a faster decline in bone mineral density with an increased risk of osteoporotic fractures	In menopausal patients, a baseline densitometry is recommended when starting endocrine therapy. Depending on the results, patients should be referred to a Bone Metabolism Service or follow ASCO/ESMO recommendations [16, 17]. Patients who are given aromatase inhibitors should receive calcium and vitamin D supplements. If osteoporosis is detected, add bone resorption inhibitors Recommend aerobic exercise Quit smoking
Joint pain	This is a very common side effect, particularly in patients treated with aromatase inhibitors	Increase frequency and duration of physical exercise Minor analgesics Acupuncture can be beneficial
Limited mobility of the scapulohumeral joint on the same side as the breast lesion	One side effect that can present long term following axillary radiation is decreased mobility of the scapulohumeral joint on the side that received radiation secondary to fibrosis in the pectoral muscle of the side affected [18]	Moderate, but constant physical exercise in the limb that received radiation On occasion, if improvement is not seen, the help of Rehabilitation Specialists should be requested
Overweight	Weight gain is common during treatment for breast cancer, especially in women in whom menopause is induced or who follow hormone deprivation treatment Furthermore, overweight has been recognized, not only as a risk factor for breast cancer but also as an unfavorable factor for relapse [19]	Monitor and control weight Low calorie diets Physical exercise (150 min/week) Psychological support
Cardiotoxicity and other vascular toxicities		Control concomitant diseases (hypertension, diabetes, obesity) Promotion of healthy lifestyles Refer to cardiology if signs of heart failure appear
	Yearly incidence of ventricular dysfunction of approximately 9% that exceeds 40% in patients over the age of 75 years or having prior heart disease
	Toxicity due to anthracyclines is sometimes detected late and is more serious and often irreversible compared to toxicity due to trastuzumab [20], which tends to be reversible
	Toxicity secondary to anthracyclines is unusual if cumulative doses of 250 mg/m2 of adriamycin or 550 mg/m2 of epirubicin [3, 21] are not exceeded
	Cardiotoxicity due to trastuzumab usually appears during the active treatment phase and indicates that treatment must be withdrawn, although a high percentage of cases recover without sequelae. In women who have presented heart failure, there is no complete evidence as to whether it is possible to discontinue long-term cardiological treatment [22–24]
	Deep-vein thrombosis (DVT) or pulmonary thromboembolism can be a side effect of tamoxifen and, less often, of aromatase inhibitors	If deep-vein thrombosis develops, refer patient to the oncologist to evaluate the advisability of continuing endocrine treatment
	In patients who have received complementary radiation therapy, especially in the case of tumors on the left side and when the internal mammary chain has been radiated, long-term follow up must be carried out, given the risk of late cardiac toxicity. Nevertheless, the more modern radiation techniques with three-dimensional planning and dose intensity modulation have made it possible to lower the incidence of this type of side effect [25, 26], although risk factors should be strictly controlled and the advisability of stress testing should be assessed [15]
Neurotoxicity	This is a side effect associated with the administration of taxanes. Sensory neurotoxicity in the form of paresthesia and pain in the hands and feet causes great discomfort	Detect toxicity early There is no specific treatment Duloxetine, gabapentin, and pregabalin can improve symptoms
Ocular toxicity	Though uncommon, tamoxifen can increase the risk of cataracts	Refer to ophthalmologist if symptoms of blurry vision appear
Asthenia	Asthenia is a highly prevalent symptom in breast cancer that often persists after competing treatments [27] The use of a visual numeric scale is recommended to quantify the degree of asthenia and should be monitored	Rule out organic cause Psychoemotional support Physical activity
Cognitive impairment	Although there are few studies, many patients report memory loss or losing the ability to concentrate after chemotherapy that can last more than 20 years after treatment Methods are being investigated that enable us to diagnose and follow-up on this side effect	Assessment by Neurology Concentration and visual memory exercises Reading
Skin changes (dryness, alopecia, others)	Following treatment with chemotherapy, some women do not recover all their hair or present side effects of the skin and related structures, such as the nails	Evaluation by Dermatologist
Risk of second neoplasms	Patients who have undergone radiation therapy are at increased risk for a second neoplasm related to treatment with radiation. This phenomenon usually occurs many years after having received radiotherapy. The tumors that appear most often are neoplasms of the lung or angiosarcomas of the chest wall [28, 29]	Factors related to lung cancer should be avoided, especially with respect to smoking