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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.

The for breast cancer -- surgery, radiation therapy (RT), hormone therapy, chemotherapy, and targeted therapies -- have been a boon to patients with breast cancer and their healthcare providers, especially as these treatments have become more refined and personalized.

But adverse events (AEs) are still an issue with all these approaches, including the potential for long-term AEs that may affect the whole body -- cardiovascular (CV), bone, lymphatic system, neuropathy, and neurologic, such as cognitive dysfunction. Other far-reaching AEs are pain and fatigue, sexual health, and emotional and psychological well-being. There is also the possibility for metabolic syndrome or secondary cancers.

"Breast cancer survivors coping with a high comorbidity burden experience worse overall quality of life [QOL] and emotional health following treatment," explained Jennifer Brooks, PhD, and Jasleen Arneja, MPH, of the University of Toronto in California in a study. "This highlights the importance of integrating information on comorbidities into survivorship care to improve the experience and overall outcomes of patients with complex needs."

Dawn L. Lovelace CNM, DNP, of Frontier Nursing University in Hyden, Kentucky, and colleagues stressed in a that primary care clinicians are likely to care for breast cancer survivors and should be familiar with common symptoms, treatment, and best practices to avoid permanent dysfunction.

CV Complications

RT and certain chemotherapy drugs, such as anthracyclines, can increase the , including the possibility of , and . The recommends a multimodal approach to managing CV health in all cancer patients that includes management of nutrition, weight, blood pressure, diabetes, and lipid levels, with exercise as the cornerstone.

Osteoporosis and Bone Health

Breast cancer survivors are at increased risk of osteoporosis due to hormonal therapies such as aromatase inhibitors or premature, chemotherapy-induced menopause. The healthcare team should monitor bone mineral density (BMD) and provide appropriate interventions as needed.

"Osteoporosis associated with breast cancer is mainly linked to estrogen deprivation induced by chemotherapy and hormone therapy, and more specifically, to the use of non-steroidal aromatase inhibitors," explained Alvaro Rodriguez-Lescure, MD, PhD, of Hospital General Universitario de Elche in Alicante, Spain, and colleagues, in .

The team urged the assessment of low BMD in people who have undergone breast cancer therapy, as these patients often present with premature loss of bone mass that contributes to the risk of osteoporosis, even in the absence of menopause.

Lymphedema

Surgery and RT can damage the lymphatic system. "Approximately 1 in 5 women treated for breast cancer are affected by breast cancer-related lymphedema, a distressing side effect distinguished by interstitial protein-rich fluid accumulation and/or regional swelling," said Melissa Troester, PhD, of the University of North Carolina at Chapel Hill, and colleagues, in .

Lymphedema is an ongoing concern for those who have undergone breast cancer treatment, even years after initial therapy. "Point prevalence of breast cancer-related lymphedema was 6.8% at baseline, and 19.9% and 23.8% at 2 and 7 years after diagnosis, respectively," the team said.

Cognitive Dysfunction

Some people who have received breast cancer treatment may have cognitive impairments -- i.e., "chemo brain." If needed, healthcare providers may undertake or refer these patients for cognitive rehabilitation.

"Postchemotherapy cognitive impairment was found in 15-25% of patients with breast cancer," noted Florence Joly, MD, and Marie Lange, PhD, of Centre Hospitalier Universitaire de Caen in France, in . Although these disorders are mild and transient for the majority of patients and abate within 6-12 months post-treatment, some patients have persistent impairment even 10 to 20 years later.

Emotional and Psychological Well-Being

Long-term survivors of breast cancer may experience emotional and psychological challenges, including anxiety, depression, fear of recurrence, and body image issues. Healthcare providers may offer psychosocial support or referral to mental health professionals, as needed.

"The prevalence of fatigue and depression has been carefully studied in patients with and survivors of breast cancer, and research suggests that approximately one third of survivors report significant symptoms of fatigue and that 20-30% report elevated depressive symptoms," wrote Julienne E. Bower, PhD, of the University of California, Los Angeles, and co-authors in the .

Of concern is a finding that in women with a mental health comorbidity (OR 1.33, 95% CI 1.06-1.68), and that this type of comorbidity was associated with a significantly increased hazard of mortality (HR 1.49, 95% CI 1.02-2.18).

Pain and Fatigue

Chronic pain and fatigue are common among people who have been treated for breast cancer, even years after completion. have identified young age, previous comorbidities (such as back pain, arthritis, osteoarthrosis, and fibromyalgia), and combined treatment (such as surgery, chemotherapy, and RT) as risk factors for chronic pain.

A person's emotional well-being may also be a predictor of susceptibility to chronic pain post-treatment. "Patient-related psychiatric and psychological risk predictors such as post-traumatic stress disorder, low mood, and anxiety commonly coexist and influence development of breast cancer-related pain," stated Lisa Doan, MD, of NYU Grossman School of Medicine in New York City, and colleagues in a recent

also appears to play a role, as a body mass index (BMI) over 30 may indicate that a person is more likely to experience chronic pain as a result of breast cancer treatment compared with those with a BMI less than 30.

Lifestyle changes such as a healthy diet, an exercise routine combining aerobic and resistance training, and ceasing smoking appear to reduce pain intensity and improve quality of life.

"Cancer-related fatigue is one of the most burdensome and potentially long-lasting effects of breast cancer treatment," explained Ines Vaz-Luis, MD, PhD, of Institut Gustave Roussy in Villejuif, France, and co-authors in the . Their research found that patient populations at higher risk of cancer-related fatigue include those who are more fragile at the time of diagnosis – including being young, having lower socioeconomic status, not having a partner, having higher BMI, having comorbidities, being a smoker, presenting heavier psychologic distress (depressive and anxiety symptoms), and concomitant symptom burden – and receiving chemotherapy and/or endocrine therapy.

More troubling, up to half of those who have received breast cancer treatment for cancer-related fatigue.

Sexual Health Concerns

Breast cancer treatments can impact sexual function and fertility. Healthcare providers should provide support, counseling, and offer potential interventions such as hormone replacement therapy or fertility preservation options, where appropriate.

"Common breast cancer treatments, including surgery, chemotherapy, radiation therapy, and hormone therapy, may result in induced menopause and decrease vaginal lubrication, affecting sexual excitement and desire," explained Javier Jerez-Roig, PhD, MPH, of the Institute for Research and Innovation in Life Sciences and Health in Central Catalonia, Spain, and colleagues in .

Nearly 80% of people with breast cancer reported they had at least between their diagnosis and 4 years of follow-up, while less than half of the people with sexual concerns reported the use of supportive care strategies, including gynecological or psychological consultations.

"Breast cancer survivors should be considered at high risk for sexual difficulties, because preexisting health conditions may worsen, and new sexual health problems often develop," advised Suneela Vegunta, MD, of the Mayo Clinic in Scottsdale, Arizona, and colleagues in the. Patients should be queried "early and frequently by their healthcare team regarding their sexual health," the authors said.

Metabolic Syndrome

Some people who have undergone breast cancer therapy may develop a cluster of conditions known as metabolic syndrome, including obesity, high blood pressure, abnormal lipid levels, and insulin resistance, which increases the risk of cardiovascular disease and type 2 diabetes. Healthcare providers will want to monitor these patients' metabolic parameters and promote healthy lifestyle changes, where appropriate.

"Recent studies have shown that metabolic syndrome and its related components exert a significant impact on the initiation, progression, treatment response, and prognosis of breast cancer," said Kunwei Shen, MD, of Shanghai Jiao Tong University School of Medicine, and colleagues, in . "Metabolic abnormalities not only increase the disease risk and aggravate tumor progression but also lead to unfavorable treatment responses and more treatment side effects."

A recent study found that (up to 43%) in breast cancer patients and were associated with higher risk (OR 1.647, 95% CI 1.139-2.382) of developing recurrent metastatic disease, particularly among those who are postmenopausal.

"Breast cancer survivors undergo an onslaught of adverse treatment-associated side effects, such as gains in body weight, reductions in physical activity, and deteriorating metabolic profiles leading to an elevated risk of cardiovascular disease and metabolic syndrome," stated Christina M. Dieli-Conwright, PhD, MPH, of Stanford University School of Medicine, in California, and colleagues, in . "Breast cancer patients who underwent (neo)adjuvant chemotherapy experienced persistent metabolic dysregulation as noted by the exacerbation of metabolic syndrome, body composition, and glucose metabolism from immediately following chemotherapy to approximately 5 years following the completion of chemotherapy."

Subsequent/Secondary Primary Cancers

Some treatments may increase the risk of developing subsequent primary cancer such as leukemia or other solid tumors. "Specifically after breast cancer radiation, a number of tissues are vulnerable to radiation damage and have increased risk for developing secondary malignancies including lung cancer, esophageal cancer, and contralateral breast cancer," observed Wataru Ebina, MD, of Perlmutter Cancer Center in New York City, and colleagues in .

Secondary primary cancer risk may also be related to the type of breast cancer. The risk of new cancers among survivors was 20% higher for those with hormone receptor (HR)-positive cancers and 44% higher for those with HR-negative cancers, reported Hyuna Sung, PhD, of the American Cancer Society in Atlanta, and colleagues in . "The higher risk after HR-negative cancer was driven by acute non-lymphocytic leukemia and breast, ovarian, peritoneal, and lung cancers."

Follow-Up and Survivor Care

The establishment of a survivorship care plan for those who have undergone breast cancer treatment includes regular follow-up visits and screening for long-term comorbidities. As nearly half of those who have undergone breast cancer treatment suffer from at least one severe post-treatment symptom, a is of great importance in mitigating potential treatment-related comorbidities as well as providing optimal, quality care.

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

Part 9: The Key Role of Primary Care Providers in Managing Breast Cancer Tx-Related AEs

Part 10: Case Study: Patient with Rare Breast Cancer Has Surprising Response to NAC