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"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

Primary care providers play a crucial role in helping manage the side effects of breast cancer treatment. Working alongside oncologists and other specialists, primary care physicians can monitor patients undergoing breast cancer treatment to assess for any adverse events (AEs) or complications and provide symptomatic relief for such common side effects as nausea, fatigue, pain, and neuropathy.

Educating breast cancer patients about the potential side effects of their treatment, what to expect, and when to seek medical attention for concerning symptoms reinforces the patient's active role in therapy. For example, endocrine therapy and targeted therapy are delivered over a longer period of time and may have long-term side effects such as osteoporosis, joint pain, and potential cardiovascular issues.

Offering guidance and direction on healthy lifestyle choices such as diet, exercise, and smoking cessation can help mitigate some side effects and improve overall well-being and quality of life (QoL).

In addition, a primary care provider may offer referrals to counselors and support groups to help patients cope with the emotional and psychological effects of breast cancer treatment.

Coordinating care among the different specialists involved in a patient's breast cancer treatment will ensure that all aspects of their health are addressed comprehensively. If specialized care is needed for a particular side effect or complication, primary care providers can refer their breast cancer patients to appropriate specialists for diagnosis and treatment.

AEs Related to Endocrine Therapy

Breast cancer patients taking endocrine therapy (ET) may receive it for 5-7 years or longer. As such, even low-grade AEs may and may worsen QoL.

Up to 94% of patients , and 20-50% of women discontinue endocrine therapy before completing the recommended 5 years of treatment.

Each class of anti-endocrine agent has . Although most of these will be managed by oncologists, over the years of treatment a patient may present to other healthcare professionals, who may assist with appropriate multidisciplinary interventions.

Although ET-related AEs can vary depending on the medication used, include flushing, sweating, and feelings of warmth, similar to menopausal symptoms; vaginal dryness, discharge, and bleeding; and sexual dysfunction. There is a high potential for bone loss; in addition, patients may have arthralgias, and there could be significantly increased tendon thickness and carpal tunnel syndrome.

is of concern, as are weight gain and diabetes, fatigue, and ocular toxicity.

such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs) such as venlafaxine, or anticonvulsants such as gabapentin or pregabalin may be prescribed to help manage hot flashes.

Non-hormonal agents are preferred for the management of vaginal dryness, dyspareunia, and dysuria, as the safety of estrogen-based agents in breast cancer patients is not definitely established.

Vitamin D/E suppositories, vaginal lidocaine, as well as vaginal lubricants and moisturizers can help alleviate discomfort.

has shown some success on overall sexual functioning, sexual desire, sexual arousal, vaginal lubrication, discomfort during sex, sexual distress, and body image observed immediately post-treatment for breast cancer.

ET, due to its prolonged use and , negatively impacts bone health. note that there is a two- to four-fold increase in bone loss compared with physiologic postmenopausal bone mineral density loss among women with breast cancer receiving ET.

As such, the guidelines recommend a careful assessment of fracture risk of both pre- and post-menopausal patients receiving ET. A dual-energy x-ray absorptiometry (DXA) scan should be offered at baseline; and then every 2 years or more frequently if deemed medically necessary.

A is crucial for bone health; when possible, physical activity should be increased, including balance training, weight-bearing, flexibility, or stretching exercises, to reduce the risk of fractures caused by falls. Vitamin D and calcium supplements should be encouraged, as well as smoking cessation and reducing alcohol consumption.

Pharmacological interventions available for among patients undergoing ET are bisphosphonates and denosumab. Also, for hormone-positive breast cancer these agents have an adjuvant benefit in reducing disease recurrence.

For arthralgia, switching to a different aromatase inhibitor may help reduce pain, and a consistent aerobic exercise program can improve musculoskeletal symptoms and QoL. Acupuncture has also been shown to help relieve musculoskeletal symptoms

The is increased by a factor of 2-3 in older women receiving ET with tamoxifen; this risk may be further pronounced when to 10 years.

Older women on tamoxifen should , such as swelling, pain, or redness in the legs, and contact their healthcare provider as soon as possible if symptoms develop.

One-third of people receiving ET report that persist in long-term follow-up, with no difference across age groups. Emphasizing regular physical activity and dietary changes may help control weight gain.

Active ET is a significant risk factor for among breast cancer survivors. Preventative strategies focused on lifestyle modifications may minimize the risk.

More than half of women on ET report , with those 55 and younger significantly more likely to have fatigue as well as patients who are overweight or have obesity. Incorporating physical activity and making dietary changes may reduce the linked with ET and may improve other related symptoms such as insomnia or anxiety.

Cross-sectional objective tests show an incidence of in about one-third to one-half of people receiving ET for breast cancer. Active for dry-eye disease and symptoms will help patients receive appropriate therapy, such as artificial tears and lubricants. If there is still no improvement, patients should be referred to ophthalmology.

AEs Related to Targeted Therapy

Among the many targeted therapies for breast cancer are HER2-based therapies, AKT inhibitors, CDK 4/6 inhibitors, mTOR inhibitors, tyrosine kinase inhibitors, and PI3KCA inhibitors. AEs vary, depending on the specific medication. Among the most common:

• affect up to 80% of patients. Topical corticosteroids or moisturizers can help alleviate skin irritation. Antihistamines and topical steroids may be considered. Adjusting the dosage or temporarily discontinuing the targeted therapy may be necessary in severe cases.

• Cardiotoxicities: Certain targeted therapies, particularly HER2 inhibitors, can affect the heart. The death of cardiomyocytes occurs through multiple pathways including HER2 blocking and the increase of reactive oxygen products. Dual-target combination therapy can more the HER2 signaling pathway that maintains normal function on cardiomyocytes, leading to cardiomyocyte apoptosis. The effect of HER2-targeted therapy-related cardiotoxicity is dose-independent and mostly reversible, which belongs to type II cardiotoxicity. Cardiologists may monitor cardiac function regularly through tests such as echocardiograms. Adjustments in medication dosage or treatment regimen may be required to manage cardiac AEs.

• can include diarrhea, nausea, vomiting, abdominal pain, and bloating, with elderly patients and those with metastatic disease experiencing the highest frequency. Certain targeted therapies may affect and in some cases, liver damage.

• Fatigue is a common AE. Engaging in light physical activity, ensuring adequate sleep, and maintaining a balanced diet, can all .

• Drug-induced pneumonitis is thought to be related to a direct or indirect cytotoxic effect, oxidative injury from free oxygen radicals, or immune-mediated mechanisms. includes cessation or dose reduction, immunosuppressive therapy, and supportive measures.

• Insulin-related AEs: Targeted therapy for breast cancer can have a dual effect on insulin by reducing the secretion of insulin from the pancreatic islet cells, essentially acquired type 1 diabetes mellitus (T1DM), or inducing insulin resistance by mechanisms similar to those in type 2 diabetes mellitus. The treatment of type 1 diabetes is similar to standard-of-care practice in which insulin is initiated at the time of diagnosis. If the patient develops type 2 diabetes as a , treatment can be initiated with consultation with an endocrinologist, who may recommend lifestyle changes, metformin, or oral hypoglycemic agents with or without insulin, depending on the degree of hyperglycemia.

• are also a possibility, since some targeted therapies can suppress bone marrow function, leading to low levels of white blood cells, red blood cells, or platelets. Again, dose may be needed.

Immunotherapy

Immunotherapy for breast cancer, particularly immune checkpoint inhibitors (ICIs) such as pembrolizumab (Keytruda), can have AEs. These are typically related to the immune system becoming overactive and attacking healthy tissues.

Frequent immune-related AEs include gastrointestinal, endocrine, and dermatologic toxicities. There are also possible neurotoxic, cardiotoxic, and pulmonary toxicities that can be fatal.

• Pulmonary AEs related to immunotherapy include interstitial lung disease and concomitant pneumonitis, with an incidence of approximately 3-5%.

• Gastrointestinal immune-related AEs, particularly , are among the most commonly reported.

• Dermatologic toxicities related to immunotherapy are very common -- often resulting in . Topical or systemic corticosteroids may be considered for treatment, depending on the severity of the condition, and discontinuation of the immunotherapy may be necessary.

• are also well documented, with the most common being acute hypophysitis and thyroid dysfunction. The is also frequently affected, with some ICIs increasing the risk of diabetes. Pituitary dysfunction and are also possible.

• , although rare, have also been reported. In CAR T-cell therapy, however, neurotoxicity is one of the most common and dangerous complications; others are (CRS) and hematologic abnormalities such as B cell aplasia, hypogammaglobulinemia, anemia, and thrombocytopenia. Immune effector cell-associated neurotoxicity syndrome () is a clinical and neuropsychiatric syndrome that can occur in the days to weeks following administration of certain types of immunotherapy, especially immune effector cell and T cell engaging therapies. Patients at include those who are younger or have pre-existing neurological/medical conditions, high tumor burden, high-intensity lymphodepleting therapy, cytopenias, and early/severe CRS.

• Cardiotoxicity has been most frequently reported with the use of . documented in this setting include atrial fibrillation, supraventricular arrhythmias, ventricular arrhythmias, and heart blocks. Treatment may include high-dose IV steroids, immunosuppressants, plasmapheresis, and IV immunoglobulins. Cessation of the immunotherapy may also be considered.

Additional helpful information is available in the of the Society for Immunotherapy of Cancer.

Surgical Therapy

Surgical therapy for breast cancer typically involves procedures such as lumpectomy or mastectomy. These surgeries can have various AEs, both short-term and long-term.

Long-term physical changes include anatomic changes, chronic pain, phantom breast pain, axillary web syndrome, and lymphedema. People who have undergone breast cancer surgery may have decreased strength, aerobic capacity, or mobility; fatigue; and cognitive dysfunction.

related to surgery include depression, anxiety, fatigue, concerns about body image, and issues with sexuality. Treatment options include physical therapy for persistent pain in the breast area, arm, and shoulder. Treatment for emotional and psychosocial changes include counseling and anti-depressive treatment. Neuropathic pain management with gabapentin, or pregabalin, acupuncture can also be used.

Radiation Therapy

Radiation therapy AEs can vary depending on the individual and the . Radiation therapy-related dermatitis, chest wall and breast pain, moist and dry desquamation, and fatigue are among the most common side effects. Lymphedema may also occur, particularly if the lymph nodes are treated.

is more frequent among patients receiving radiation therapy for left-sided rather than right-sided breast tumors. Radiotherapy has made impressive advances in the second half of the 20th century with technological development continuing in the 21st century. Although the target volume doses remain the same, modern radiotherapy techniques have significantly and major coronary vessels.

Chemotherapy

Some of the common short-term AEs of breast cancer chemotherapy include fatigue, nausea, vomiting, diarrhea, alopecia, neutropenia, thrombosis, and stomatitis.

Before starting chemotherapy, all patients receiving anthracycline or HER2-based therapies should undergo a baseline cardiologic evaluation with an electrocardiogram and echocardiography. Patients should be reassessed at the end of treatment and every 6 months for the first year post-therapy.

Short-term AEs typically ; the duration of treatment has a major impact on the total side effect burden. Most adjuvant treatment regimens last approximately 4-6 months, although some are shorter.

of chemotherapy include cardiotoxicity, premature ovarian failure, premature menopause, bone marrow dysfunction such as myelodysplastic syndromes, and rarely leukemia.

Read previous installments in this series:

Part 1: Breast Cancer -- The Basics of Diagnosis, Staging, and Treatment

Part 2: Breast Cancer: Making the Diagnosis With Breast Biopsy

Part 3: What to Know About Management of Early-Stage Breast Cancer

Part 4: New Treatment Options for Locally Advanced and Metastatic Breast Cancer

Part 5: Genetic Testing in Breast Cancer: Mutations, Multigene Panels, and More

Part 6: Case Study: Older Male With Rash, Chest Swelling, and Mysterious Skin Issues

Part 7: Breast Cancer Palliative Care and Metastatic Disease: Looking Beyond End of Life

Part 8: Breast Cancer and Post-Surgical Screening: Advising Patients on Appropriate Imaging