CARING FOR BREAST CANCER SURVIVORS

November 16, 2012

Karen L. Smith MD, MPH Attending Physician, Division of Hematology/Medical

Oncology, Washington Hospital Center

Assistant Professor of Medicine, Georgetown University

Dislosure

• Consulting for Genomic Health

Learning Objectives

• Understand the unique medical and psychosocial needs of breast cancer survivors.

• Apply current practice guidelines for managing breast cancer survivors in the primary care setting.

• Understand the purpose of Breast Cancer Survivorship Programs.

CASE STUDY

49 year old obese female with PMH significant for HTN. She is s/p breast conserving surgery with axillary lymph node dissection, chemotherapy (anthracycline and taxane-containing) and whole breast radiation for T2N1M0 stage IIB L breast cancer. Her tumor was ER/PR +, her2 negative. She has chemotherapy induced amenorrhea and is currently taking Tamoxifen.

CASE STUDY

• What long-term risks does she face after breast cancer treatment?

– Recurrence risk

– Risk of new primary cancers

– Risk of treatment-related toxicities

• To what follow-up schedule should she adhere? With which doctors should she follow-up?

• What type of imaging studies are appropriate for this patient?

PRE-TEST

Please complete the baseline knowledge assessment handed out at the entrance. Please pass it to the end

of your row when complete.

CARING FOR BREAST CANCER SURVIVORS

• OUTLINE:

– Definition of a “survivor”

– Scope of the problem

– Elements of survivorship care, survivorship care plans and models for providing survivorship care

– Clinical issues in caring for breast cancer survivors

DEFINING “SURVIVOR”

DIFFERING DEFINITIONS

• Moment of diagnosis

• Completion of initial treatment

• Living 5 years beyond diagnosis

• Dying from a cause other than cancer

Hewitt M, Greenfield S, Stovall E. From Patient to Cancer Survivor: Lost in Transition. Washington DC: National Academies Press; 2006.

SCOPE OF THE PROBLEM • Lifetime risk of breast cancer 12.3% (1 in 8 women)

– Most common cancer in women

• 230, 480 estimated new female breast cancer cases in 2011

• 39,520 estimated deaths due to breast cancer in women in 2011

• As of January 1, 2012, there were 2,971,610 women alive with a history of breast cancer

http://www.seer.cancer.gov/statfacts/html/breast.html. Downloaded January 13, 2012 Siegel, R et al. Cancer Statistics, 2011: The Impact of Eliminating Socioeconomic and Racial Disparities on Premature Cancer Deaths. CA: A Cancer Journal for Clinicians. 2011;61:212-236. Siegel, R eg al. Cancer Treatment and Survivorship Statistics, 2012. CA: A Cancer Journal for Clinicians. 2012;62:220-241

STAGE DISTRIBUTION AND SURVIVAL RATE BY STAGE AT DIAGNOSIS (2001-2007)

Stage at Diagnosis Stage Distribution (%)

5-year Relative Survival (%)

Localized 60% 98.6%

Regional 33% 83.8%

Distant 5% 23.3%

Unknown 2% 52.4%

http://www.seer.cancer.gov/statfacts/html/breast.html Downloaded January 13, 2012

INSTITUTE OF MEDICINE (IOM) & CANCER SURVIVORSHIP

• IOM established committee to examine medical and psychosocial issues faced by cancer survivors

• Recommendations made to improve survivors’ health care and quality of life

• Issued report in 2006 focusing on survivors of adult cancer during the phase of care that follows primary treatment: From Cancer Patient to Cancer Survivor: Lost in Transition

Hewitt M, Greenfield S, Stovall E. From Patient to Cancer Survivor: Lost in Transition. Washington DC: National Academies Press; 2006.

INSTITUTE OF MEDICINE REPORT: “LOST IN TRANSITION”

4 ELEMENTS OF SURVIVORSHIP CARE

1) Prevention of recurrent and new cancers, and of late effects of treatment

2) Surveillance for cancer metastasis, recurrence, or second cancers; assessment of medical & psychosocial late effects

3) Intervention for consequences of cancer and its treatment

4) Coordination between specialists and primary care providers to ensure that all of the survivor’s health needs are met.

Hewitt M, Greenfield S, Stovall E. From Patient to Cancer Survivor: Lost in Transition. Washington DC: National Academies Press; 2006, p. 3.

SURVIVORSHIP CARE PLANS

IOM Recommendation:

“Patients completing primary treatment should be provided with a comprehensive care summary and follow-up plan that is clearly and effectively explained. This “Survivorship Care Plan” should be written by the principal provider(s) who coordinated oncology treatment. This service should be reimbursed by third-party payors of health care.”

Hewitt M, Greenfield S, Stovall E. From Patient to Cancer Survivor: Lost in Transition. Washington DC: National

Academies Press; 2006, p. 4.

IOM RECOMMENDATIONS: COMPONENTS OF A BREAST CANCER SURVIVORSHIP CARE PLAN

• Names and phone numbers of oncology care providers • Family history of cancer; genetic testing results (if applicable) • Pathology of tumor; staging • Type of treatment received: surgery, radiation, chemotherapy

(associated toxicities, dose received), endocrine therapy • Potential late / long-term effects of treatments received • Follow-up care schedule for first 5 years after treatment: oncology

visits, mammograms, DEXA scans • Recommendations for cancer screenings: colonoscopy, pap smear • Health maintenance recommendations: diet, exercise, bone health,

eye health, skin health, mental health / well-being • Signs / Symptoms of recurrence, metastasis or new primary cancer • Psychosocial resources

Hewitt M, Greenfield S, Stovall E. From Patient to Cancer Survivor: Lost in Transition. Washington DC: National Academies Press; 2006.

PROVIDING SURVIVORSHIP CARE: SHARED CARE

• Coordinated effort between health care providers

• Primary responsibility for patient care transitions from oncologist back to primary care provider at a certain point in patient’s cancer care

• Ongoing exchange of information between providers with oncologist available for consults

• Survivorship Care Plans may help facilitate this transfer of care between providers

Peairs KS, Wolff AC, Olsen SJ, et al. Coordination of care in breast cancer survivors: An overview. The Journal of Supportive Oncology. 2011;9:210-215.

CLINCICAL ISSUES IN CARING FOR BREAST CANCER SURVIVORS

• Key components:

– Surveillance for disease recurrence or new primary breast cancers

– Management of late / long-term effects of local therapy and systemic therapy

– Screening for other malignancies

– Lifestyle modification

– Psychosocial support

– Patient education

SUGGESTED FOLLOW-UP FOR BREAST CANCER SURVIVORS

• American Society of Clinical Oncology (ASCO) 2006 Guidelines: – H&P every 3-6 mo for yrs 1-3 post-treatment, then

every 6-12 mo for yrs 4-5 post-treatment • National Comprehensive Cancer Network (NCCN) 2012

Guidelines: – H&P every 4-6 mo for 5 years post-treatment, then

annually

Khatcheressian JL, Wolff AC, Smith TJ, et al: American Society of Clinical Oncology 2006 update of the breast cancer follow-up and management guidelines in the adjuvant setting. Journal of Clincial Oncology. 2006;24:5091-5097. National Comprehensive Cancer Network: Guidelines Version 3.2012 – Invasive breast cancer. Available at www.nccn.org. Accessed October 8, 2012.

BREAST CANCER SUVIVORS: BREAST CANCER RECURRENCE RISKS

• Risk of metastases from original tumor

• Risk of developing an in-breast recurrence after breast conserving treatment

• Risk of developing a new primary breast cancer (ipsilateral or contralateral)

– Often difficult to distinguish in-breast recurrence from ipsilateral new primary breast cancer

RISK OF DISTANT METASTATIC DISEASE

• Risk of developing metastases and death due to breast cancer varies with time and according to characteristics of the tumor

• Overall, the annual hazard rate for breast cancer death peaks 2-3 years after diagnosis

• Risk of early recurrence and death greater for estrogen receptor negative tumors

• Risk of later recurrence and death greater for estrogen receptor positive tumors

Jatoi I, Anderson WF, Jeong JH et al. Breast Cancer Adjuvant Therapy: Time to Consider Its Time-Dependent Effects. Journal of Clinical Oncology 2011;29:2301-2304.

Annual hazard rates for breast cancer death and ER-negative to ER-positive hazard ratios

(Table 1) using the National Cancer Institute's Surveillance, Epidemiology, and End Results 13

Registries Databases (1992 to 2007) for invasive female breast cancer.

Jatoi I et al. JCO 2011;29:2301-2304

©2011 by American Society of Clinical Oncology

SURVEILLANCE FOR DISTANT METASTASES • Metastatic disease often presents with symptoms between

regularly scheduled visits

• Common sites of metastases include bone, lung, liver, CNS

• Routine labs, tumor markers and scans to detect metastases are not recommended

– Randomized trials demonstrate no survival benefit or quality of life benefit for early detection of distant metastases through intensive surveillance programs compared to standard clinical follow-up.

Karam, AK. Breast cancer post-treatment surveillance: Diagnosis and management of recurrent disease. Clinical Obstetrics and Gynecology. 2011;54:157-163 Impact of follow-up testing on survival and health-related quality of life in breast cancer patients. A multicenter randomized controlled trial. The GIVIO Investigators. JAMA 1994;271:1587-92. Rosselli Del Turco M, Palli D, Cariddi A et al. Intensive diagnostic follow-up after treatment of primary breast cancer. A randomized trial. National Research Council Project on Breast Cancer follow-up. JAMA 1994;271:1593-7. Pali D, Russo A, Saieva, C et al. Intensive vs. clinical follow-up after treatment of primary breast cancer: 10-year update of a randomized trial. JAMA. 1999;281:1586

RISK OF IN-BREAST TUMOR RECURRENCE AND NEW PRIMARY BREAST CANCER IN

BREAST CANCER SURVIVORS • Risk of new primary breast cancers/in-breast tumor

recurrences greater in women with a personal history of breast cancer than in general population

• In-breast tumor recurrence/new primary ipsilateral breast cancer: – 10 year risk after breast conserving therapy 7.7%

– 25 year risk after breast conserving therapy approx 20%

• New primary contralateral breast cancer – 25 year risk approx 10-15% (yearly estimate 0.5-1%)

Simone NL, Dan T, Shih J et al. Twenty-five year results of the national cancer institute randomized breast conservation trial. Breast Cancer Research and Treatment 2011. Epub ahead of print. Early Breast Cancer Trialists’ Collaborative Group. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10 801 women in 17 randomised trials. The Lancet. 2011;378:1707-16.

SURVEILLANCE FOR IN-BREAST RECURRENCE OR NEW PRIMARY BREAST CANCERS: BREAST IMAGING

• Mammograms:

– ASCO Guidelines:

• First post-treatment mammogram no earlier than 6 mo after radiation

• Subsequent mammograms every 6-12 mo

• Yearly mammograms if findings stable after completion of locoregional treatment

Khatcheressian JL, Wolff AC, Smith TJ, et al: American Society of Clinical Oncology 2006 update of the breast cancer follow-up and management guidelines in the adjuvant setting. Journal of Clinical Oncology. 2006;24:5091-5097

SURVEILLANCE FOR IN-BREAST RECURRENCE OR NEW PRIMARY BREAST CANCERS: BREAST IMAGING

• Breast MRI:

– No evidence to suggest screening MRI improves outcomes in asymptomatic patients with a history of breast cancer

– Majority of data supporting screening MRI based on populations with family history and/or deleterious genetic mutations

– Insufficient data to recommend for or against MRI in women with a personal history of breast cancer

Karam, AK. Breast cancer post-treatment surveillance: Diagnosis and management of recurrent disease. Clinical Obstetrics and Gynecology. 2011;54:157-163 Saslow D, Boetes C. Burke W et al. American Cancer Society Guidelines for Breast Screening with MRI as an Adjunct to Mammography. CA Cancer J Clin 2007;57:75-89. National Comprehensive Cancer Network: Guidelines Version 1.2012 –Breast Cancer Screening and Diagnosis. Available at www.nccn.org. Accessed October 8, 2012

POST-MASTECTOMY SURVEILLANCE

• Incidence of locoregional recurrence after mastectomy low (2-10%) and constitutes metastatic disease.

– Risk varies with age, stage, response to therapy and receipt of post-mastectomy radiation

• Insufficient evidence to either support or counter post-mastectomy surveillance imaging

• No specific guidelines address imaging for women who have undergone mastectomy and breast reconstruction

Zakihreh J, Fowble B, Esserman LJ, et al. Application of screening principles to the reconstructed breast. Journal of Clinical Oncology. 2010;28:173-180. Barnsley GP, Grunfeld, E, Phil, D et al. Surveillance mammography following the treatment of primary breast cancer with breast reconstruction: A systematic review. Plastic & Reconstructive Surgery. 2007;120:1125-1132.

LATE / LONG-TERM EFFECTS OF LOCAL THERAPY

• Local therapies include: – Surgery:

• Mastectomy or partial mastectomy

• Axillary sentinel lymph node biopsy with or without axillary lymph node dissection

– Radiation: • Whole breast irradiation (usually includes axillary lymph

nodes)

• Boost to tumor bed

• Supraclavicular lymph nodes included in high risk patients

LATE LONG-TERM EFFECTS OF LOCAL THERAPY: COMPLICATIONS OF SURGERY

• Seroma formation

• Anatomic distortion

• Pain / numbness of breast, chest wall, or axilla

• Decreased mobility ipsilateral arm

• Lymphedema

Chalasani P, Downey L, Stopeck AT. Caring for the breast cancer survivor: A guide for primary care physicians. The American Journal of Medicine. 2010;123:489-495

LATE / LONG-TERM EFFECTS OF LOCAL THERAPY: LYMPHEDEMA

• Incidence

– 10-40%

• Pathophysiology

– Increased osmotic pressure due to functional overload of the lymphatic channels

– Chronic low-grade inflammation causes fibrosis and disorganized collagen fibers, causing hardening of tissues and functional deficits

– Incompetent lymphatic valves cause further stasis

• Symptoms:

– Edema, feeling of heaviness, tightness or aching to the affected arm, axilla or ipsilateral chest wall

Chalasani P, Downey L, Stopeck AT. Caring for the breast cancer survivor: A guide for primary care physicians. The American Journal of Medicine. 2010;123:489-495

LATE / LONG-TERM EFFECTS OF LOCAL THERAPY: LYMPHEDEMA RISK FACTORS

• Extent of axillary lymph node surgery

– Risk much smaller with sentinel lymph node biopsy (approximately 5%) than axillary dissection

• Radiation therapy

• Obesity, weight gain after treatment

• Skin infection/injury

• Airline travel

Chalasani P, Downey L, Stopeck AT. Caring for the breast cancer survivor: A guide for primary care physicians. The American Journal of Medicine. 2010;123:489-495 Norman SA, Localio AR, Potashnik SL, et al. Lymphedema in breast cancer survivors: Incidence, degree, time course, treatment and symptoms. Journal of Clinical Oncology. 2009;27:390-397 Partridge AH, Winer EP, Burstein, HJ, et al. Follow-up care of breast cancer survivors. Seminars in Oncology. 2003;30:817-25

Norman SA, Localio AR, Potashnik SL, et al. Risk factors for lymphedema after breast cancer treatment. Cancer Epidemiology Biomarkers and Prevention 2010;19: 2734-46. McLaughlin SA, Wright MJ, Morris KT, et al. Prevelance of lymphedema in women with breast cancer 5 years after sentine lymph node biopsy or axillary dissection: Objective measurement. Journal of Clinical Oncology. 2008;26:5213-5219.

LATE / LONG-TERM EFFECTS OF LOCAL THERAPY: LYMPHEDEMA

Treatment – Physiatry consult

– Compression sleeves

– Pneumatic compression pump

– Massage

– Physical therapy/exercise

Prevention – Avoid trauma to arm (including

venipuncture, BP cuff, injections, IV medications)

– Treat infections, injuries promptly

– Good skin and nail care

– Avoid constricting sleeves or jewelry

– Wear compression sleeve for airplane travel and heavy exertional activity of the arm

– Avoid extreme heat or cold (including baths/hot tubs)

Chalasani P, Downey L, Stopeck AT. Caring for the breast cancer survivor: A guide for primary care physicians. The American Journal of Medicine. 2010;123:489-495 Partridge AH, Winer EP, Burstein, HJ, et al. Follow-up care of breast cancer survivors. Seminars in Oncology. 2003;30:817-825

LATE LONG-TERM EFFECTS OF LOCAL THERAPY: COMPLICATIONS OF RADIATION

• Radiation pneumonitis

• Rib fracture

• Brachial plexopathy

• Fibrosis

• Cardiotoxicity

• Secondary malignancies

LATE / LONG-TERM EFFECTS OF LOCAL THERAPY: RADIATION PNEUMONITIS

• Inflammation of lung tissue due to irradiation. • Acute (4-12 wks after treatment) or late (6-12 mo after treatment) • Incidence depends on dose and field, but overall incidence is low (<5%) • Risk factors:

– Increasing lung volume in the tangent fields – Treatment to the supraclavicular, axillary , & internal mammary

regions vs. breast only (4.1% vs. 0.9%) • Management:

– Steroids, pulmonary evaluation

Lingos TI, Recht A, Vicini F, et al. Radiation pneumonitis in breast cancer patients treated with conserative surgery and radiation therapy. International Journal Radiation Oncology Biology Physics. 1991;21:355-360. Lind PA, Marks LB, Hardenbergh PH, et al. Technical factors associated with radiation pneumonitis after local +/- regionial radiation therapy for breast cancer. International Journal Radiation Oncology Biology Physics. 2002;1:137-143.

LATE / LONG-TERM EFFECTS OF LOCAL THERAPY: RIB FRACTURE FOLLOWING RADIATON THERAPY

• Risk is low: < 3% • Median time to develop rib fracture 1 year. • Higher incidence with radiation doses exceeding 50 Gy (standard dose 50.4 Gy plus 10 Gy boost) and use of

concomitant chemotherapy

Pierce SM, Rech A, Lingos TI, et al. Long-term radiation complications following conservative surgery and radiation therapy in patients with early stage breast cancer. International Journal Radiation Oncology Biology Physics. 1992;23:915-923. Meric F, Buchholz TA, Mirza NQ, et al. Long-term complications associated with breast-conservation surgery and radiotherapy. Annals of Surgical Oncology. 2002;9:543-549.

LATE / LONG-TERM EFFECTS OF LOCAL THERAPY: BRACHIAL PLEXOPATHY

• Caused by radiation therapy and /or axillary surgery • Shoulder, arm, hand can be affected

– Neuropathic pain, paresthesias, weakness • Risk low: 1% of women receiving < 50 Gy to the

supraclavicular and axillary fields – Higher risk when > 50Gy radiation dose delivered to axillary

area, concurrent chemotherapy administration, and use of a third field

• Management: – Neurology – Physiatry

Pierce SM, Rech A, Lingos TI, et al. Long-term radiation complications following conservative surgery and radiation therapy in patients with early stage breast cancer. International Journal Radiation Oncology Biology Physics. 1992;23:915-923.

LATE / LONG-TERM EFFECTS OF LOCAL THERAPY: RADIATION-INDUCED BREAST FIBROSIS

• Skin retraction, induration, thickening, pain

• Challenging clinical breast exam

• Occurs in approximately 1/3 of patients treated with breast conserving surgery and radiation

• Occurs more frequently when treated with additional radiation fields and larger tumor size

Funda M, Buchholz TA, Mirza NQ, et al. Long-term complications associated with breast-conserving surgery and radiotherapy. Annals of Surgical Oncology. 2002;9:543-549.

LATE / LONG-TERM EFFECTS OF LOCAL THERAPY: RADIATION-INDUCED CARDIOTOXICITY

• May not manifest for > 10 years after radiation

• May include pericardial disease, CAD, cardiomyopathy, CHF, valvular disease, conduction abnormalities

• Older radiation techniques definitely associated with cardiotoxicity – especially for L side and if internal mammary lymph nodes included in field

• Contemporary radiation techniques minimize radiation to the heart

– Recent studies of associations between current radiotherapy techniques and risk of cardiotoxicity inconclusive

Hooning MJ, Botma A, Aleman B, et al. Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. Journal of the National Cancer Institute. 2007;99:365-375. Gutt R, Correa CR, Hwang WT, et al. Cardiac morbidity and mortality after breast conservation treatment in patients with early-stage breast cancer and pre-existing cardiac disease. Clincal Breast Cancer 2008;8:443-8.

LATE / LONG-TERM EFFECTS OF LOCAL THERAPY: SECONDARY MALIGNANCIES AFTER BREAST IRRADIATION

• Non-breast malignancies (lung cancer, sarcoma, leukemia)

– Excess risk of a secondary non-breast malignancy compared to women who do not receive radiation approx 1%

• Contralateral breast cancer

– Controversial whether breast irradiation increases risk of contralateral breast cancer

Galper S, Gelman R, Recht A, et al. Second nonbreast malignancies after conservative surgery and radiation therapy for early-stage breast cancer. International Journal Radiation Oncology Biology Physics. 2002;1:406-414. Clarke M, Collins R, Darby S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;12:2087-2106. Hooning, MJ, Berthe MP, Aleman MH, et al. Roles of radiotherapy and chemotherapy in the development of contralateral breast cancer. Journal of Clinical Oncology. 2008;26:5561-5568.

LATE / LONG-TERM EFFECTS OF SYSTEMIC THERAPY

• Systemic therapies for early stage breast cancer include: – Chemotherapy

• Anthracyclines

• Cyclophosphamide

• Taxanes

– Her2 targeted therapy • Trastuzumab

– Endocrine therapy • Tamoxifen (pre-menopausal or post-menopausal)

• Aromatase inhibitors (AI) (post-menopausal)

LATE / LONG-TERM EFFECTS OF CHEMOTHERAPY

• Fatigue/Cognitive dysfunction

• Neuropathy

• Cardiotoxicity

• Chemotherapy-induced amenorrhea, premature menopause

• Secondary malignancies

LATE / LONG-TERM EFFECTS OF CHEMOTHERAPY: FATIGUE

• “Cancer-related fatigue is a distressing persistent, subjective sense of physical, emotional and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning” – NCCN Guidelines

• Incidence 26%-90% • May persist for up to 10 years after treatment ends. • Perceived as one of the most pervasive and debilitating

symptoms of cancer – affects emotional & physical well-being, relationships,

employment

National Comprehensive Cancer Network: Guidelines Version 1.2012 –Cancer-Related Fatigue. Available at www.nccn.org. Downloaded January 13, 2012. Wanchai A, Armer JM, & Stewart, BR. Nonpharmacologic supportive strategies to promote quality of life in patients experiencing cancer-related fatigue: A systematic review. Clinical Journal of Oncology Nursing. 2011;15:203-214.

LATE / LONG-TERM EFFECTS OF CHEMOTHERAPY: FATIGUE

General Management of Fatigue

• Self-monitoring of fatigue

• Energy conservation

Non-pharmacologic Interventions

• Initiation of exercise program

• Consider referral to physiatry

• Psychotherapy (cognitive behavioral)

• Nutrition consultation

• Sleep hygiene

Pharmacologic Interventions

• Consider stimulants AFTER ruling out other causes of fatigue

National Comprehensive Cancer Network: Guidelines Version 1.2012 –Cancer-Related Fatigue. Available at www.nccn.org. Downloaded January 13, 2012.

LATE / LONG-TERM EFFECTS OF CHEMOTHERAPY: COGNITIVE DYSFUNCTION

• Many breast cancer survivors report subjective sense of cognitive dysfunction (“chemo brain”)

• Difficult to separate cognitive dysfunction from anxiety, depression, fatigue, effects of hormonal changes

• Neuropsychological testing has not consistently revealed difference in cognitive function between breast cancer patients and healthy controls – However, one recent small study demonstrated cognitive

impairment with associated white matter changes on MRI 3-5 mo after chemo

• No proven interventions for prevention or treatment Debess J, Riis JO, Engebjerg MC, et al. Cognitive function after adjuvant treatment for early breast cancer: a population-based longitudinal study. Breast Cancer Research and Treatment. 2010;121:91-100. Azim HA, De Azambuja E, Colozza M et al. Long-term toxic effects of adjuvant chemotherapy in breast cancer. Annals of Oncology. 2001;22:1939-1947 Ganz PA. “Doctor, Will the Treatment You are Recommending Cause Chemobrain?” Journal of Clinical Oncology. 2012;30:229-31. Deprez S, Amant F, Smeets A et al. Longitudinal Assessment of Chemotherapy-Induced Structural Changes in Cerebral White matter and Its

Correlation with Impaired Cognitive Functioning. Journal of Clinical Oncology. 2012;30:274-81.

LATE / LONG-TERM EFFECTS OF CHEMOTHERAPY: NEUROPATHY

• Associated with taxane use (paclitaxel, docetaxel)

• Peripheral sensory nerves most commonly affected

– Neuropathic pain, paresthesias

– Symptoms typically symmetrical

• Incidence is dose dependent

• More common in patients with pre-existing nerve damage (e.g. diabetes)

• May resolve or become chronic

Farquhar-Smith P. Chemotherapy-induced neuropathic pain. Current Opinion in Supportive and Palliative Care. 2011;5:1-7.

LATE / LONG-TERM EFFECTS OF CHEMOTHERAPY: MANAGEMENT OF NEUROPATHY

The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain – Evidence Based Guidelines

• 1st Line Treatment (can be used alone or in combination)

– Tricyclic anti-depressants – SSNRIs – Gabapentin or pregabalin – Topical lidocaine

• Consider referral to physiatry or pain management specialist .

Dworkin RH, O’Connor AB, Audette J et al. Recommendations for the pharmacological management of neuropathic pain: An overview and literature update. Mayo Clinic Proceedings. 2010;85:S3-S14

LATE / LONG-TERM EFFECTS OF CHEMOTHERAPY: CARDIOTOXICITY

Anthracyclines (doxorubicin or epirubicin) • Damage myocardial cells by generating free radicals • May take mo-yrs for symptoms to appear • Risk dose dependent • Incidence of CHF 5% for doxorubicin with cumulative dose of

approx 400 mg/m2 • Risk factors: old age, hypertension, pre-existing CAD, previous

mediastinal radiation therapy, concomitant trastuzumab, diabetes, black

• Avoid in patients with low LVEF at baseline

Azim HA, de Azambuja E, Colozza M, et al. Long-term toxic effects of adjuvant chemotherapy in breast cancer. Annals of Oncology. 2011;22:1939-1947. Pinder MC, Duan A, Goodwin JS et al. Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer. Journal of Clinical Oncology 2007;25:3808-15.

Congestive heart failure in patients treated with doxorubicin: Dose Response

Swain SM, Whaley FS, Ewer MS. Cancer. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003;97:2869-79.

LATE / LONG-TERM EFFECTS OF CHEMOTHERAPY: CHEMOTHERAPY-INDUCED AMENORRHEA (CIA)

• Risk of CIA depends on age, type of chemotherapy, and total number of cycles of chemotherapy

• Menses may recur late, however most women who remain amenorrheic 1 year following treatment will not regain ovarian function.

• Women who resume menstruation after chemotherapy likely have reduced fertility and may experience menopause at an earlier age

Partridge AH, Winer, EP, Burstein HJ. Follow-up care of breast cancer survivors. Seminars in Oncology. 2003;30:817-825. Azim HA, De Azambuja E, Colozza M, et al. Long-term toxic effects of adjuvant chemotherapy in breast cancer. Annals of Oncology. 2011;22:1939-1947

Bleeding after chemotherapy by patient age

Petrek J A et al. JCO 2006;24:1045-1051

©2006 by American Society of Clinical Oncology

Bleeding after chemotherapy by type of regimen

Petrek J A et al. JCO 2006;24:1045-1051

©2006 by American Society of Clinical Oncology

LATE / LONG-TERM EFFECTS OF CHEMOTHERAPY: CHEMOTHERAPY-INDUCED AMENORRHEA

• Amenorrhea ≠ Infertility

• Amenorrhea ≠ Menopause

– Difficult to assess menopausal status in women with CIA

• Issues in managing premature menopause after chemotherapy:

– vasomotor symptoms

– vaginal dryness

– loss of bone mineral density

– cardiovascular health

• Issues resulting from chemotherapy-induced premature menopause may be exacerbated by hormonal therapy for breast cancer

Ganz P. Breast cancer, menopause, and long-term survivorship: Critical issues for the 21st century. The American Journal of Medicine. 2005;118:136S-141S. National Comprehensive Cancer Network: Guidelines Version 3.2012 –Breast Cancer. Available at www.nccn.org. Accessed October 8, 2012.

LATE / LONG-TERM EFFECTS OF CHEMOTHERAPY: CHEMOTHERAPY-INDUCED AMENORRHEA

• Vaginal atrophy

– Minimal data available to guide management

– Generally try to avoid hormonal therapy

• Non-hormonal lubricants

• Non-hormonal vaginal moisturizers

– If necessary, consider local hormonal therapy with minimal systemic absorption after discussion of potential risks related to estrogen absorption

• Estradiol vaginal ring

ACOG Practice Bulletin. Management of Gynecologic Issues in Women with Breast Cancer. Obstetrics and Gynecology. 2012;119(666-682)

OBSTETRIC ISSUES IN BREAST CANCER SURVIVORS

• Fertility may be impaired even after recovery from CIA • Data inconsistent regarding whether pregnancy outcomes inferior • No difference in 5-year overall survival for women with stage I-II

breast cancer who became pregnant after treatment • Avoidance of pregnancy recommended for first few years after

breast cancer treatment – Balance risk of cancer recurrence with pregnancy goals

• Avoidance of pregnancy required during tamoxifen • Non-hormonal contraception required for breast cancer survivors

– Copper IUD recommended • Lactation may be impaired after breast irradiation (due to fibrosis)

Azim HA, De Azambuja E, Colozza M et al. Long-term toxic effects of adjuvant chemotherapy in breast cancer. Annals of Oncology. 2001;22:1939-1947 Langagergaard V, Gislum M, Skriver MV et al. Birth outcome in women with breast cancer. British Journal of Cancer. 2006;94:142-146. Dalberg K, Eriksson J, Holmberg L. Birth outcome in women with previously treated breast cancer – a population-based cohort study from Sweden. PloS Med 2006;3:e336 Averett HE, Mirhashemi R, Moffat FL. Pregnancy after breast carcinoma: The ultimate medical challenge. Cancer. 1999;85:2301-2304 Chalasani P, Downey L, Stopeck AT. Caring for the breast cancer survivor: A guide for primary care physicians. The American Journal of Medicine. 2010;123:489-495. Tralins AH. Lactation after conservative breast surgery combined with radiation therapy. American Journal of Clinical Oncology. 1995;18:40-43. Moran MS, Colasanto JM, Haffty BG, et al. Effects of breast-conserving therapy on lactation after pregnancy. The Cancer Journal. 2005;11:399-403. Azim HA Jr, Bellettini G, Liptrott SJ et al. Breastfeeding in breast cancer survivors: Pattern, behaviour and effect on breast cancer outcome. Breast. 2010;19:527-531. ACOG Practice Bulletin. Management of Gynecologic Issues in Women with Breast Cancer. Obstetrics and Gynecology. 2012;119(666-682)

LATE / LONG-TERM EFFECTS OF CHEMOTHERAPY AND ENDOCRINE THERAPY: MANAGEMENT OF

VASOMOTOR SYMPTOMS • Mild symptoms: behavioral modifications

• Severe symptoms :

– Venlafaxine

– Gabapentin

– Clonidine

• Estrogen therapy is generally contraindicated in breast cancer survivors

• No evidence to support efficacy & long-term safety of phytoestrogens and black cohosh

Pachman DR, Jones JM, Loprinzi CL. Management of menopause-associated vasomotor symptoms: Current treatment options, challenges and future directions. International Journal of Womens Health. 2010;9:123-135. Loprinzi CL, Kugler JW, Sloan JA et al. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomized controlled trial. The Lancet. 2000;356:2059-63. Boekhout AH, Vincent AD, Dalesio OB et al. Management of hot flashes in patients who have breast cancer with venlafaxine and clonidine: a randomized, double-blind, placebo-controlled trial. Journal of Clinical Oncology. 2011;29:3862-8 Thacker HL. Assessing risks and benefits of nonhormonal treatments for vasomotor symptoms in perimenopausal and postmenopausal women. Journal of Womens Health. 2011;7:1007-16.

RISK OF CHEMOTHERAPY-INDUCED MDS/AML IN BREAST CANCER SURVIVORS

• Alkylating agents and anthracyclines can cause myelodysplastic syndrome (MDS) & acute myeloid leukemia (AML)

– Alkylating agents: 5-10 years after initial treatment

– Anthracyclines: 1-5 years after initial treatment

• Risk of AML/MDS after anthracycline-containing breast cancer chemotherapy 0.3-1.2%

Azim HA, De Azambuja E, Colozza M, et al. Long-term toxic effects of adjuvant chemotherapy in breast cancer. Annals of Oncology. 2011;22:1939-1947. Smith RS, Bryant J, DeCillis A. Acute myeloid leukemia and myelodysplastic syndrome after docorubicin-cyclophosphamide adjvuvant therapy for operable breast cancer: the national surgical adjuvant breast and bowel project experience. Journal of Clinical Oncology 2003;21:1195-1204. Praga C, Bergh J, Bliss J et al. Risk of acute myeloid leukemia and myelodysplastic syndrome in trials of adjvuant epirubicin for early breast cancer: correlation with doses of epirubicin. Journal of Clinical Oncology. 2005;23:4179-91.

CARDIOTOXICITY OF TRASTUZUMAB

• Initial studies of trastuzumab + chemotherapy in metastatic setting revealed 9.2% risk of cardiac dysfunction (range 1-27%, highest with concurrent anthracyclines)

• Risk observed in adjvuant studies of trastuzumab lower (2-14%)

– Risk lowest when trastuzumab given with non-anthracycline containing adjuvant chemotherapy (0.4%)

• Often reversible: Can treat CHF medically and rechallenge with trastuzumab

Seidman A, Hudis C, Pierri MK et al. Cardiac dysfunction in the trastuzumab clinical trials experience. Journal of Clinical Oncology. 2002;20:1215-21 Piccart-Gebhart MJ, Procter M, Leyland-Jones B et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. New England Journal of Medicine. 2005;353:1659-1672. Romond EH, Perez EA, Bryant J et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. New England Journal of Medicine. 2005;353:1673-1684. Slamon D, Eiermann W, Robert N et al. Adjuvant Trastuzumab in Her2-Positive Breast Cancer. New England Journal of Medicine. 2011;365:1273-83. Ewer MS, Vooletich MT, Durand JB et al. Reversibility of Trrastuzumab-Related Cardiotoxicity: New Insights Based on Clinical Course and Response to Medical Treatment. Journal of Clinical Oncology 2005;23:7820-7826. Azim HA, de Azambuja E, Colozza M, et al. Long-term toxic effects of adjuvant chemotherapy in breast cancer. Annals of Oncology. 2011;22:1939-47

LATE/LONG TERM EFFECTS OF ENDOCRINE THERAPY

• Tamoxifen – Thromboembolism

– Endometrial cancer

– Drug interactions

– Vasomotor symptoms

• Aromatase Inhibitors (AI) – Arthralgias

– Loss of bone mineral density (BMD)

– Vasomotor symptoms

LATE / LONG-TERM TOXICITY OF TAMOXIFEN: THROMBOEMBOLISM

• DVT/PE, stroke

– Approximately 2-fold increased risk of DVT/PE

• Risk primarily in women > 50 years

– Small increased risk of stroke

– Absolute risks of thromboembolic events < 1%

• Consider holding tamoxifen prior to elective surgery and resuming when patient ambulatory

Braithwaite RS, Chlebowski RT, Lau J. Meta-analysis of vascular and neoplastic evens associated with tamoxifen. Journal of General Internal Medicine. 2003;18:937-947. Fisher B, Costantino JP, Wickerham DL et al. Tamoxifen for Prevention of Breast Cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. JNCI. 1998;90:1371-88 EBCTCG. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365:1687-1717. Hayes DF. Follow-up of patients with early breast cancer. The New England Journal of Medicine. 2007; 356:2505-2513.

LATE / LONG-TERM TOXICITY OF TAMOXIFEN: ENDOMETRIAL CANCER

• Tamoxifen has estrogenic effects on the endometrium • Risk of endometrial cancer for women taking tamoxifen

2/1000 per year • Usually early stage • Abnormal bleeding should be promptly evaluated in women

on tamoxifen • Routine endometrial biopsy and US not recommended for

women on Tamoxifen (high false positive rate of US)

EBCTCG Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. The Lancet 2005 365:1687-1717 Endometrial Ca Risk 0.19% / year Chalasani P, Downey L, Stopeck AT. Caring for the breast cancer survivor: A guide for primary care physicians. The American Journal of Medicine. 2010;123:489-495 Fisher B, Costantino JP, Wickerham DL et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. JNCI 1998;90:1371-88. Braithwaite RS, Chlebowski RT, Lau J. Meta-analysis of vascular and neoplastic evens associated with tamoxifen. Journal of General Internal Medicine. 2003;18:937-947. ACOG Practice Bulletin. Management of Gynecologic Issues in Women with Breast Cancer. Obstetrics and Gynecology. 2012;119(666-682)

TAMOXIFEN: DRUG INTERACTIONS

Sideras K, Ingle JN, Ames MM, et al. Coprescription of tamoxifen and medications that inhibit CYP2D6. Journal of Clinical Oncology. 2010;28:2768-2776.

-Tamoxifen is a pro-drug -Primary and secondary metabolism by the cytochrome P450 system generates more potent metabolites, such as endoxifen -CYP2D6 is the rate limiting enzyme required for the generation of endoxifen -Medications that inhibit CYP2D6 may reduce endoxifen concentrations and may reduce tamoxifen efficacy

TAMOXIFEN: DRUG INTERACTIONS Commonly used anti-depressants which inhibit CYP2D6:

• Moderate-potent inhibitors – paroxetine

– fluoxetine

– bupropion

– duloxetine

• Weak-moderate inhibitors – sertraline

– citalopram

– fluvoxamine

Alternatives to consider: • venlafaxine

• desvenlafaxine

• reboxetine

• escitalopram

• mirtazapine

* Co-prescription of strong or intermediate CYP2D6 inhibitors with tamoxifen should be avoided if alternate drugs are available Sideras K, Ingle JN, Ames MM, et al. Coprescription of tamoxifen and medications that inhibit CYP2D6. Journal of Clinical Oncology. 2010;28:2768-2776.

LATE / LONG-TERM TOXICITY OF AROMATASE INHIBITORS: ARTHRALGIAS

• Reported rates approximately 5-40% • Usually small joints • Management:

– Non-pharmacoclogic: weight-bearing exercise, stretching, joint mobility exercises, physical therapy, acupuncture / acupressure, transcutaneous electrical nerve stimulation, moist heat, massage

– Pharmacologic: acetaminophen, NSAIDs, Cox2 inhibitors, tramadol, pain modifiers (nortriptyline, gabapentin, pregabalin)

– Repleting Vitamin D, if deficient, may improve arthralgias – Consider changing from one aromatase inhibitor to another – Refer to rheumatologist if refractory

Thorne C. Management of arthralgias associated with aromatase inhibitor therapy. Current Oncology. 2007;14 (supplement 1):S11-S19. Rastelli AL, Taylor ME, Gao F et al. Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomized trial. Breast Cancer Research and Treatment. 2011;129:107-16.

LATE / LONG-TERM TOXICITY OF AROMATASE INHIBITORS: LOSS OF BONE MINERAL DENSITY

• AIs cause loss of BMD

• Multiple AI trials demonstrate ↑ risk of fracture with AI therapy

– 5-year fracture risk approx 7-10%

– No reported cases of osteoporosis in patients with normal baseline BMD

– Risk factors for AI-associated fracture: age, baseline osteoporosis, tobacco use, prior bone fracture, prior HRT

Howell A, Cuzick J, Baum M, et al. 2005 Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet. 2005;365:60-62. Coates AS, Keshaviah A, Thurlimann B, et al. 2007 Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. Journal of Clinical Oncology. 2007;25:486-492. Coleman RE, Banks LM, Girgis SI et al. Skeletal effects of exemestane on bone-mineral density, bone biomarkers, and fracture incidence in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES): a randomised controlled study. The Lancet Oncology. 2007;8:119-27. Eastell R, Adams JE, Coleman RE et al. Effect of Anastrozole on Bone Mineral Density: 5-Year Results From the Anastrozole, Tamoxifen, Alone or in Combination Trial 18233230. Journal of Clinical Oncology. 2008;26:1051-57 Rabaglio M, Sun Z, Price KN et al. Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial. Annals of Oncology. 2009;20:1489-98.

LATE / LONG-TERM TOXICITY OF AROMATASE INHIBITORS: LOSS OF BONE MINERAL DENSITY

• Concurrent initiation of zoledronic acid and AI reduces loss of BMD in comparison to later initiation of zoledronic acid

• Denosumab reduces loss of BMD with AI therapy

• No evidence for reduced risk of fracture for early administration of bisphosphonates or denosumab

• Bisphosphonates may also improve breast cancer outcomes

• Timing of initiation of bone-targeted therapy and choice of therapy controversial

Denosumab package insert. Available at www.proliahcp.com. Accessed January 29, 2012. Brufskky AM, Harker WG, Beck JT et al. Final 5-year results of Z-FAST trial: Adjuvant Zoledronic Acid Maintains Bone Mass in Postmenopausal Breast Cancer Patients Receiving Letrozole. Cancer. 2011; epub ahead of print. Accessed online January 29, 2012. Gnant M, Mlineritsch B, Luschin-Ebengreuth G et al. Long-Term Follow-Up in ABCSG-12: Significantly Improved Overall Survival with Adjuvant Zoledronic Acid in Premenopausal Patients with Endocrine-Receptor–Positive Early Breast Cancer. Cancer Res. 2011;71(24 Suppl):Abstract S1-2. De Boer R, Bundred N, Eidtmann H et al. Long-Term Survival Outcomes among Postmenopausal Women with Hormone Receptor-Positive Early Breast Cancer Receiving Adjuvant Letrozole and Zoledronic Acid: 5-Year Follow-Up of ZO-FAST. Cancer Resesarch. 2011;71(24 Suppl): Abstract S1-3.

Patient with breast cancer

initiating or receiving Al therapy

T-Score > -2.0 No

additional risk factors

T-Score < -2.0 Any 2 of the following risk factors:

• T-score <-1.5

• Age > 65 years

• Low BMI (<20 kg/m2)

• Family history of hip fracture

• Personal history of fragility fracture

after age 50

• Oral corticosteroid use of

> 6 months

• Smoking (current and history of)

Exercise, Calcium and

vitamin D supplements

Monitor risk status and

BMD

Bisphosphonates

therapy, calcium and

vitamin D supplements,

exercise

Monitor BMD

Hadji P, Aapro MS, Body JJ et al. Management of aromatase inhibitor-associated bone loss in postmenopausal women with breast

cancer: practical guidance for prevention and treatment. Annals of Oncology. 2011;22:2546-55.

A Proposed Algorithm for Initiation of

Bisphosphonate Therapy During AI Therapy

SCREENING FOR NEW NON-BREAST CANCERS IN BREAST CANCER SURVIVORS

• 50-70% of new cancers are non-breast cancers

• Approximately 20% greater risk of new primary non-breast malignancies compared to general population

• No data to support enhanced screening for non-breast malignancies

• No data to support screening for radiation- and chemotherapy-induced malignancies

• Routine age-appropriate screening

Schaapveld M, Visser O, Louwman MJ, et al. Risk of new primary nonbreast cancers after breast cancer treatment: A Dutch population-based study. Journal of Clinical Oncology. 2008;8:1239-1246. Simone NL, Dan T, Shih J et al. Twenty-five year results of the national cancer institute randomized breast conservation trial. Breast Cancer Research and Treatment 2011. Epub ahead of print.

LIFESTYLE MODIFICATIONS FOR BREAST CANCER SURVIVORS

• Women who are overweight after diagnosis and treatment face ↑ risk of breast cancer recurrence and death compared to women of normal weight

• Prospective observational data demonstrates exercise reduces breast cancer mortality (>25 observational studies)

• Women’s Healthy Eating and Living Study (randomized trial) demonstrated improved breast cancer survival with exercise and high vegetable-fruit intake

• Exercise decreases breast cancer-specific concerns (improved health related quality of life)

• More prospective randomized controlled trials assessing effect of lifestyle modifications on breast cancer outcomes are needed

Holmes MD, Chen WY, Feskanich D, et al. Physical activity and survival after breast cancer diagnosis. The Journal of the American Medical Association. 2005;293:2479-2486. Ballard-Barbash R, Friedenreich CM, Courneya KS et al. Physical activity, biomarkers, and disease outcomes in cancer survivors: a systematic review. JNCI. 2012; 104:815-40). Chlebowski RT, Aiello E, McTiernan A. Weight loss in breast cancer patient management. Journal of Clinical Oncology. 2002;20:1128-1143. McTiernan A, Irwin M, VonGurenigen V. Weight, physical activity, diet, and prognosis in breast and gyencologic cancers. Journal of Clinical Oncology. 2010; 28:4074-4080. Kwan ML, Kushi LH, Weltzien E et al. Alcohol consumption and breast cancer recurrence and survival among women with early –stage breast cancer: The life after cancer epidemiology study. Journal of Clinical Oncology. 2010;28:4410-16. Pierce, JP, Stefanick ML, Flatt SW et al. Greater survival after breast cancer in physically active women with high vegetable-fruit intake regardless of obesity. Journal of Clinical Oncology. 2007;10:2345-2351. Mishra S, Scherer RW, Geigle PM et al. Exercise interventions on health-related qualify of life for cancer survivors. Cochrane Database Syst Rev. 2012.

PSYCHOSOCIAL ISSUES IN BREAST CANCER SURVIVORS

• Psychosocial problems common in breast cancer survivors, especially younger survivors

• Issues include: – Anxiety

– Depression

– Fear of recurrence

– Altered body image

– Relationship issues

– Sexual dysfunction

• Must inquire about psychosocial concerns and offer counseling and/or pharmacologic intervention

Ganz PA. Breast cancer, menopause, and long-term survivorship: critical issues for the 21st century. The American Journal of Medicine. 2005;118:136S-141S Partridge AH, Winer EP, Burstein HJ. Follow-up Care of Breast Cancer Survivors. Seminars in Oncology. 2003;30:817-25.

CASE STUDY

• What long-term risks does she face after breast cancer treatment?

– Recurrence risk

– Risk of new primary cancers

– Risk of treatment-related toxicities

• To what follow-up schedule should she adhere? With which doctors should she follow-up?

• What type of imaging studies are appropriate for this patient?

POST-TEST AND EVALUATION

Please complete the post-test and evaluation. Please pass it to the end

of your row when complete.

ACKNOWLEDGEMENTS • Grant Support:

– Sanofi-Aventis

• Principle Investigator: – Sandra Swain MD

• Survivorship Nurse Practitioner: • Shannon Murphy MS APRN FNP-BC

• Oncology Program Manager: – Earlene Whitaker

• Washington Cancer Institute Survivorship Committee and Clinical Team: – Medical Oncology:

• Pia Herbolsheimer MD • Sandra Swain, MD • Raquel Nunes, MD

– Breast Surgery: • Marc Boisvert MD • Lana Bijelic, MD

– Radiation Oncology: • Pamela Randolph-Jackson MD • Michael Porazzo MD • Adedamola Omogbehin MD • Ruchika Gutt MD

– Breast Imaging: • Anna Choi MD • Brooke Wolvin MD • Nicole Proscia MD

– Gynecology: • Melissa Fries MD

– Cancer Support Services: • Heather Kapp MSW

– Physiatry: • Eric Wizotsky MD

– Plastic Surgery: • Rafael Convit MD • Susan Otero MD • Praful Ramineni MD