Long-term Follow-up of Breast Cancer Patients Julie R. Gralow, M.D. Director, Breast Medical Oncology, Seattle Cancer Care Alliance Professor, Medical Oncology, University of Washington School of Medicine Member, Clinical Division, Fred Hutchinson Cancer Research Center

The Cancer Care Continuum Detection Treatment Survivorship & Diagnosis Optimal care of an individual person differs along the continuum

Institute of Medicine 2005 Report From Cancer Patient to Cancer Survivor: Lost in Transition Hewitt M, Greenfield S, and Stovall E, eds. http://www.cancer.net/patient/Survivorship/IOM_Executive_Summary.pdf Transition from active treatment to post-treatment care critical to long-term health Routine follow-up visits are opportunities to promote healthy lifestyle, check for cancer recurrence, manage lasting effects of the cancer experience Cancer survivors are a heterogeneous population, some having few late effects of cancer and its treatment, and others suffering permanent and disabling symptoms The good news is that there is much that can be be done to avoid, ameliorate, or arrest the late effects of cancer

Complications of therapy: Patient Name: UW/SCCA medical record number: Date of Birth: Cancer Diagnosis: Date of Diagnosis: Age at Diagnosis: Tumor Stage: Tumor Size (T) , Nodes (N) , Metastases (M) Tumor grade: Hormone receptors: Estrogen receptor (ER) , Progesterone receptor (PR) HER-2: IHC, FISH Oncotype DX (if done): Family History of Cancer: BRCA1/2 testing (if done): Significant Past Medical History and Medications: Cancer Treatment Surgery Breast Surgery: Procedure, date Lymph Node Surgery: Procedure, date Reconstruction: Procedure, date Systemic Therapy Chemotherapy: Route Dose Schedule Number of cycles Cumulative Anthracycline Dose Administered: Doxorubicin____ mg/m2 Epirubicin___ mg/m2 HER-2 Targeted Therapy: Drug, start date, stop date Endocrine (Hormonal Therapy): Drug, start date, stop date Bisphosphonate Therapy for Breast Cancer Indication: Drug, start date, stop date Enrolled in Clinical Trials? Radiation Therapy Date Start Date Stop Total Dose (cGy) Fields included: Complications of therapy: Providers Primary Care Provider: Surgeon: Radiation Oncologist: Medical Oncologist: IOM Report: All Patients Should Receive a Cancer Treatment Summary SCCA Breast Cancer Treatment Summary (modified from asco.org)

Breast Cancer Follow-Up Includes Three Major Goals: Surveillance for cancer recurrence Monitoring for toxicities related to therapy Maximizing overall health and quality of life

Breast Cancer Survivorship Care Plan (modified from asco.org) Follow-Up Care Test Recommendation Medical history and physical Visit your doctor every three to six months for the first three years after the first treatment, every six to 12 months for years four and five, and every year thereafter. Post-treatment breast imaging The SCCA recommends a mammogram of the affected breast every 6 months for up to 3 years from cancer diagnosis, and annual mammography of the opposite breast. In some selected patients, a periodic breast MRI or ultrasound may be recommended. Breast self-examination . Perform a breast self-examination every month. This procedure is not a substitute for a mammogram. Inspection and palpation of irradiated skin and soft tissues every year. Report any unusual symptoms to your medical provider. Pelvic examination Continue to visit a gynecologist regularly. Women taking tamoxifen should report any irregular vaginal bleeding to their doctor. Laboratory tests Your oncologist will determine which blood tests are recommended in your case. This may include a periodic complete blood count (CBC), chemistry panel, liver and kidney tests, and tumor markers. Radiology tests Your oncologist will determine which radiology tests are recommended in your case. While a regular chest xray is sometimes indicated annually in higher-risk patients, it is uncommon to routinely recommend bone scans, CT scans, PET scans or MRIs in asymptomatic patients. Every few years a DEXA scan to evaluate bone density is indicated in postmenopausal breast cancer patients. Coordination of care Most patients diagnosed with invasive breast cancer continue to be followed by their medical oncologists for at least 5 years from diagnosis. It is important to also have a primary care doctor, to manage non-cancer related health issues.

Surveillance for Breast Cancer Recurrence Local/Regional Recurrence Distant Recurrence Assessment of risk of cancer recurrence and second cancers Interventions to further reduce risk of cancer Early detection of recurrence and second cancers

Recurrence hazard rate Assessing Risk of Cancer Recurrence Recurrence Hazard Rates for Breast Cancer After Primary Therapy Saphner et al, J Clin Oncol 14:2738, 1996 0.3 0.2 Recurrence hazard rate 0.1 Saphner and colleagues analyzed the annual hazard of recurrence of over 3500 breast cancer patients after surgery. While the hazard of recurrence was greatest between years 1 and 2 after surgery and then decreased consistently until the interval between years 5 and 6, the average hazard of recurrence between years 5 and 12 was still 4.3% per year. In summary, even more than 5 years post-surgery, the risk of breast cancer recurrence remains elevated. This indicates the need for an effective treatment option in the extnded adjuvant setting. 1 2 3 4 5 6 7 8 9 10 11 12 Years

Assessing Risk of Second Cancers How Much Breast Cancer Is Hereditary? 15-20% 5-10% 70-80%

Cancer Screening: Looking for Cancer Recurrence and Second Cancers Mammography Health Professional’s Exam Self-Exam Breast MRI in some very high risk?

Monitoring for Toxicities Related to Therapy Assessing risk of toxicities Interventions to reduce risk of toxicity Detection and treatment of side effects

Side Effects of Chemotherapy Cardiac Events vs Side Effects of Chemotherapy Cardiac Events vs. Cumulative Chemotherapy Dose 100 80 Doxorubicin 60 Cardiac events (%) 40 This Kaplan-Meier plot depicts the rate of cardiac events(defined by left ventricular ejection fraction < 35) in patients with metastatic breast cancer by cumulative dose of anthracycline received. Among patients receiving Doxil (indicated by the insert color line), cumulative doses exceeding 450 mg/m2 were not associated with an increasing risk for cardiotoxicity. The risk for developing a cardiac event was significantly lower in Doxil-treated patients vs conventional doxorubicin-treated patients. Among all treated patients, at cumulative doses above 500-550 mg/m2, there was a 40% risk of developing a cardiac event with conventional doxorubicin compared with only an 11% risk with Doxil. Wigler N, et al. [abstract] Proc Am Soc Clin Oncol. 2002;21:45a. Abstract 177. 450 mg/m2 20 100 100 200 200 300 300 400 400 500 500 600 600 700 700 800 800 900 900 1000 1000 Cumulative anthracycline dose (mg/m2)

Side Effects of Chemotherapy Chemotherapy-induced Menopause in Breast Cancer Ovarian damage is a significant long-term consequence of adjuvant chemotherapy in premenopausal breast cancer patients All are affected by resultant menopausal effects Infertility seriously affects some For women who retain ovarian function after breast cancer, pregnancy is possible post-chemo Limited data do not show a worse outcome for women who become pregnant after breast cancer New techniques for preserving ovarian function and achieving fertility are under study

Side Effects of Endocrine Therapy Adjuvant Hormonal Treatment of Breast Cancer: Weighing the Side Effects Arthralgia/myalgia Neurocognition? DVT, CVA Hyperlipidemia Sexual function? Uterine CA Osteoporosis risk Cardiovascular Dz? Hot flashes Tamoxifen Aromatase Inhibitors

Assessing Risk of Side Effects Women Cancer Patients Are at Increased Risk for Osteoporosis Lack of estrogen Estrogen prevents bone breakdown (resorption) and preserves bone density Estrogen may also help maintain normal levels of vitamin D, an important nutrient in bone protection Premenopausal women Chemotherapy-induced menopause Ovarian suppression Postmenopausal women Aromatase inhibitors

Maximizing Overall Health and Quality of Life The Effects of Breast Cancer Treatment on Emotional and Physical Well-Being Fatigue/decreased energy Nausea/vomiting Alopecia (hair loss) Menopause Infertility Sexuality/body image Lymphedema Depression, anxiety Pain Fear of recurrence Etc….

Managing Menopause Prevalence of Menopausal Symptoms in Women with a History of Breast Cancer Couzi et al, JCO 1998 Hot flashes 65% Night sweats 44% Vaginal dryness 48% Pain with intercourse 26% Insomnia 44% Depression 44%

Exercise, Physical Activity and Cancer Team Survivor Northwest Mt. Baker August 2008

Exercise Decreases Side Effects During Treatment Fatigue and QOL Outcomes of Exercise During Cancer Treatment Mock V et al, Cancer Pract 9: 119-127 2001 Patients: 52 breast cancer patients randomized to home-based walking program or usual care during chemotherapy or radiation therapy Results: Women who exercised > 90 minutes per week (divided over 3 or more days) reported significantly Less fatigue Less emotional distress Higher functional ability Better QOL

Physical Activity Can Impact Breast Cancer Survival Exercise and Survival After Breast Cancer Diagnosis (Nurses Health Study) Holmes MD et al, JAMA 2005 Patients: 2,987 nurses with early stage breast cancer Physical activity categories: LOW MEDIUM HIGH Results: Compared to women with LOW physical activity, risk of dying of breast cancer was: 20% less for MEDIUM exercise (at least 3 hours per week walking at average pace) 40-50% less for HIGH exercise

What About Lymphedema?

Carefully Monitored Exercise Does Not Increase Lymphedema Weight Training and Lymphedema in Breast Cancer Survivors Ahmed RL et al, J Clin Oncol 2005 Patients: 45 breast cancer survivors s/p axillary lymph node dissection Study: Randomized to weight training program or not Weight training sessions 2x per week for 6 months For upper body, initially used no weights or only wrist weights, weight gradually increased if no symptoms of lymphedema developed Results: None of the women in the weight training program experienced a noticeable change in arm circumference (> 2 cm) Frequency of new lymphedema, or worsening of existing lymphedema, was similar in both groups

Nutrition, Body Weight and Breast Cancer -Maintain good body weight -Low fat diet -High fiber -Increase fruits and vegetables -Limit alcohol

Nutrition Can Impact Breast Cancer Survival Women’s Intervention Nutrition Study (WINS) Chlebowski R et al, 2006 Patients: 2,437 postmenopausal women with early stage breast cancer Intervention: Randomized within 1 year of surgery to: dietary intervention (8 biweekly counseling sessions by nutritionists and support throughout) vs. control Results: At 1 year: Intervention group 1/3 less fat intake per day At 5 years: 24% reduction in breast cancer recurrence Conclusion: Nutrition interventions can decrease recurrences in breast cancer patients

Weight Can Impact Breast Cancer Survival Body Weight and Breast Cancer Weight gain during adulthood has been found to be a consistent and strong predictor of breast cancer risk Overweight women (BMI > 25) are 1.3 – 2.1 times more likely to die from breast cancer compared to women with normal weight (BMI = 18.45 – 24.9)

Cognitive Function Urogenital Atrophy Premenopausal Postmenopausal

Sexuality and Body Image

Strategies for Providing Patient Support Seattle Cancer Care Alliance University of Washington Women’s Wellness Follow-up Clinic Screening for cancers Management of menopausal symptoms Screening for osteoporosis, cardiac risk factors Physical therapy Nutrition Psychology and social services Reconstructive surgery Genetic counseling Education (newsletter, lectures, retreats)

OVERALL HEALTH AND WELLNESS RECOMMEDATIONS Health Maintenance Make sure you keep up to date on vaccinations and routine health maintenance screening (cholesterol, blood pressure, skin checks, pelvic exams, colonoscopy, etc). Exercise and Physical Activity The SCCA encourages breast cancer survivors to adopt a physically active lifestyle. Try to engage in at least 30 minutes of moderate to vigorous physical activity 4-5 days of the week. Request a referral to physical therapy for help in setting goals, and/or aid in dealing with physical limitations. Lymphedema Review lymphedema prevention education. Consider a referral to physical therapy for lymphedema, range of motion, or general exercise recommendations if indicated. Nutrition The SCCA supports the nutrition guidelines of the American Cancer Society to optimize health and reduce cancer risk. These include a diet high in fruits, vegetables and whole grains, and low in fat. Choose foods and drinks in amounts that help achieve and maintain a healthy weight, and limit alcohol. Request a referral to our nutrition department if you’d like help in setting nutrition goals. Genetic counseling and testing If there is a history of cancer in your family, or if you were diagnosed with breast cancer at a very young age, consider genetic counseling and testing. Fear of Recurrence Develop and strengthen coping skills. Talk to friends and family. Request a referral to a therapist and information on community resources as needed. Heart Health Low fat diet, regular aerobic exercise and maintaining weight and blood pressure. Know what your cholesterol level is. Symptoms that should be reported are SOB, dizziness, and chest pain and new onset or worsening of fatigue. Bone Health Regular weight bearing exercise. Daily Calcium and vitamin D, limit ETOH and no smoking. Pain Regular exercise both aerobic and resistance training, stretching, yoga, acupuncture and massage can decrease pain. Fatigue Adequate sleep, regular exercise and good nutrition will facilitate recovery and reduce fatigue after treatment. Sexual Health/Body Image Communicate with your partner. Suggest vaginal lubricants/moisturizers and plan time for intimacy. Consider a referral to a therapist to address body image issues, or a gynecologist for help with vaginal atrophy and other physical issues. Memory/ cognitive concerns Look into organizational strategies such as establishing a routine and keeping a planner, taking notes, etc. Focus on addressing anxiety and depression symptoms, if present, and optimizing sleep and nutrition.

Strategies for Providing Patient Support Team Survivor Northwest An Exercise and Fitness Program for All Women Affected by Cancer Founded 1995 Weekly workouts Twice weekly walks Running Hiking Biking Yoga and tai chi Dragon boating Swimming Annual fitness retreat

Optimizing Health and Wellness After a Diagnosis of Cancer Team Survivor Northwest Dragon Boat Team The majority of cancer patients can look forward to a long life after diagnosis and treatment Clinicians must work with patients on all aspects of health and well-being: regular exercise weight control healthy diet smoking avoidance sunscreen stress reduction controlling co-morbidities: hypertension, diabetes, hyperlipidemia, osteoporosis