Beyond Diagnosis: Supporting Patients With HER2-Positive Metastatic Breast Cancer Presented by Darci Blackmon MSN, RN, OCN
©2014 Genentech USA. All rights reserved. HPK0002546700
Objectives Understand the anatomy of breast cancer metastasis and the impact of metastasis on survival Discuss the unique needs of patients diagnosed with metastatic breast cancer (MBC) Discuss the contribution of human epidermal growth factor receptor 2 (HER2) overexpression to the aggressiveness of MBC Introduce HER2 testing recommendations and methods for patients with MBC
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Epidemiology of MBC An estimated 232,340 new cases of invasive breast cancer and 64,640 cases of in situ breast cancer were diagnosed in 20131 Approximately 10% of newly diagnosed patients have metastatic disease at the time of diagnosis2 - Patients diagnosed with MBC have a poor 5-year survival rate (~ 24%) compared with patients diagnosed with early-stage breast cancer (84%99%)1 Recurrence occurs in an estimated 30% of women initially diagnosed with early-stage breast cancer3 Invasive breast cancer is more common in older women1
References: 1. American Cancer Society. Breast Cancer Facts & Figures 2013-2014. 2013. 2. Foxson SB et al. Cancer Nursing: Principles and Practice. 2011. 3. Early Breast Cancer Trialists’ Collaborative Group. Lancet. 2005;365(9472):1687-1717.
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Breast Cancer Metastasis1,2 Metastatic cascade: angiogenesis, detachment, invasion, transport, survival, and arrest/extravasation Blood vessel
Primary tumor
Detachment and invasion References: 1. Foxson SB et al. Cancer Nursing: Principles and Practice. 2011. 2. Merkle CJ. Cancer Nursing: Principles and Practice. 2011.
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Breast Cancer Metastasis1,2 Metastatic cascade: angiogenesis, detachment, invasion, transport, survival, and arrest/extravasation
Transport and survival References: 1. Foxson SB et al. Cancer Nursing: Principles and Practice. 2011. 2. Merkle CJ. Cancer Nursing: Principles and Practice. 2011.
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Breast Cancer Metastasis1,2 Metastatic cascade: angiogenesis, detachment, invasion, transport, survival, and arrest/extravasation
Secondary tumor
Arrest/extravasation
References: 1. Foxson SB et al. Cancer Nursing: Principles and Practice. 2011. 2. Merkle CJ. Cancer Nursing: Principles and Practice. 2011.
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Breast Cancer Metastasis1,2 Metastatic cascade: angiogenesis, detachment, invasion, transport, survival, and arrest/extravasation The lymphatic system is the primary route of metastasis The most common sites of metastasis include the bone, brain, lung, and liver - More than 50% of patients have metastasis to the bone Patients with MBC are considered to have stage IV cancer according to the TNM staging system
References: 1. Foxson SB et al. Cancer Nursing: Principles and Practice. 2011. 2. Merkle CJ. Cancer Nursing: Principles and Practice. 2011.
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Implications of an MBC Diagnosis Treatable, generally not curable1
5-Year Survival Rate* 100
Initial diagnosis for 10% of women with breast cancer1 5-year survival rate at diagnosis: 25%2 Survival, %
80
Symptoms often related to site(s) of metastasis1
60
40
20
0
In situ
Localized
Regional
Advanced/ metastatic Stage of Disease at Diagnosis
* Invasive breast cancer, US females, all ages, all races References: 1. Foxson SB et al. Cancer Nursing: Principles and Practice. 2011. 2. SEER cancer statistics review (CSR) 1975-2011. National Cancer Institute website.
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TNM Stage Stage I Small tumor, negative nodes
Stage II A, B* Small tumor, positive nodes Large tumor, negative nodes
Stage III A, B, C Advanced locoregional tumor
Stage IV Distant metastasis * The TNM combinations represented by stage II have been simplified for presentation purposes; please refer to the National Comprehensive Cancer Network (NCCN) guidelines.
Reference: NCCN. NCCN Guidelines for Patients: Breast Cancer. Version 2.2011.
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Treatment Goals1,2 Early Breast Cancer Treatment Goals Neoadjuvant • Downstage tumor • Increase breast
conservation rate
Advanced Disease Treatment Goals
Adjuvant • Prolong life – Improve survival – Potentially cure • Prevent recurrence
Metastatic • Prolong life – Prolong duration
of response – Delay progression
and progression
• Control symptoms
• Eliminate occult
• Optimize quality of
metastases
life
References: 1. Foxson SB et al. Cancer Nursing: Principles and Practice. 2011. 2. NCCN. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. Version 3.2014.
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Treatment Modalities1,2
Surgery
Hormonal therapy
Radiation
Targeted therapy
Chemotherapy
References: 1. Foxson SB et al. Cancer Nursing: Principles and Practice. 2011. 2. NCCN. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. Version 3.2014.
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Symptom Management
Brain
Lung
– Headache, confusion
– Cough, shortness of breath
– Nonopioid, opioid, or nonsteroidal
– Use of cough suppressants or
anti-inflammatory drugs may relieve pain1
narcotics may alleviate symptoms
Liver
Bone
– Lack of appetite, nausea, weight loss
– Persistent, deep-seated bone pain
– Appetite stimulants may help improve
– Bisphosphonate therapy may provide
appetite and increase weight gain3
palliative treatment1,2
References: 1. NCCN. NCCN Clinical Practice Guidelines in Oncology: Adult Cancer Pain. Version 2.2014. 2. Foxson SB et al. Cancer Nursing: Principles and Practice. 2011. 3. NCCN. NCCN Clinical Practice Guidelines in Oncology: Palliative Care. Version 2.2013.
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Other Considerations Education on disease diagnosis and trajectory1,2 Management of anxiety, depression, and pain2
Education on end-of-life planning3
Financial considerations1
Social support1
Nurses supporting patients and families dealing with MBC can find more information on these topics at BioOncology.com and the Genentech Access Solutions website (http://www.genentech-access.com) or by attending oncology clinical coordinator (OCC)–delivered live educational programs. References: 1. Northouse LL, Song L. Cancer Nursing: Principles and Practice. 2011. 2. Cohen MZ, Bankston S. Cancer Nursing: Principles and Practice. 2011. 3. ASCO. Advanced cancer care planning: what patients and their families need to know about their choices when facing serious illness.
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Special Considerations for Select Populations Specific populations of patients will have different needs and concerns. Age: - A metastatic diagnosis may have different implications for young women and women of childbearing age1 - Care for geriatric patients, who may have multiple comorbidities, may be more complex1 Race/ethnicity: - African American women have reduced 5-year survival rates compared with white women, attributable to a later stage at diagnosis and poorer stagespecific survival2 Socioeconomic status: - Patients with reduced access to health care (eg, patients living in rural communities, lacking health insurance, or living in poverty) have lower survival rates2 Tumor type: - Patients with HER2-positive tumors have a more aggressive disease course that may require specific treatment approaches based on high levels of evidence1 References: 1. Foxson SB et al. Cancer Nursing: Principles and Practice. 2011. 2. American Cancer Society. Breast Cancer Facts & Figures 2013-2014. 2013.
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Molecular Classifications of Breast Cancer Subtypes
-
Abbreviations: ER, estrogen receptor; PR, progesterone receptor. Reference: American Cancer Society. Breast Cancer Facts & Figures 2013-2014. 2013.
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Aggressiveness of HER2-Positive MBC HER2 protein overexpression or HER2 gene amplification is observed in approximately 20% to 25% of breast cancer cases1,2
HER2 Positivity Is Correlated With Decreased Survival1
HER2-positive status is associated with more aggressive tumor behavior and poorer patient outcomes in breast cancer1 HER2-positive status is associated with the following2: - Decreased time to recurrence - Increased risk of metastasis - Decreased overall survival a
These patients did not receive HER2-directed therapy value represents log-rank difference in cumulative survival
bP
References: 1. Witton CJ et al. J Pathol. 2003;200(3):290-297. 2. Slamon DJ et al. Science. 1987;235(4785):177-182.
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Prognostic Factors in MBC1,2
Tumor Factor
Lower Risk
Higher Risk
Hormone receptor (HR) status
Positive
Negative
HER2 status
Negative
Positive
Disease-free interval
> 2 years
< 2 years
Number of metastases
Limited
Extensive
Sites of metastases
Soft tissue/bone
Viscera
Vital organ involvement
No
Yes
HER2 remains a relevant prognostic factor independent of other prognostic factors, including node status, histopathologic grade, and HR status.2
References: 1. Burstein et al. DeVita, Hellman, and Rosenberg's Cancer: Principles and Practice of Oncology. 2011. 2. Sjörgen S et al. J Clin Oncol. 1998;16(2):462-469.
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Epidemiology of HER2-Positive MBC Advanced-stage cancer is aggressive
Numbers of Patients Newly Diagnosed with MBC Who Received Multiple Lines of Therapy3,a 9000
15% to 20% of invasive breast cancers are HER2-positive1,2 Number of Patients
As disease progresses, the number of patients receiving additional lines of therapy decreases3
HER2-directed
8000 1578
7000 6000
Chemotherapy
6189
5000 4000
772
3000
3305
2000
507 1526
1000
289
770 0 1 N = 7767
2 N = 4077
3 N = 2033
4+ N = 1059
Line of Therapy a Retrospective
longitudinal analysis of a cohort of 7767 patients diagnosed with MBC between 2005 and 2009. Patients were identified from the Truven Health MarketScan® Commercial and Medicare Supplemental Database
References: 1. Witton CJ et al. J Pathol. 2003;200(3):290-297. 2. Slamon DJ et al. Science. 1987;235(4785):177-182. 3. Ray S et al. J Comp Eff Res. 2013;2(2):195-206.
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Implications of a HER2-Positive MBC Diagnosis In HER2-positive MBC, the HER2 gene is amplified, leading to overexpression of the HER2 protein on the cell surface1,2
Normal
Prognosis: more rapid cell proliferation and increased aggressiveness in breast cancer1,2 Prediction: possible response to HER2-directed therapy2
HER2 overexpression
Excessive cellular division References: 1. Press MF et al. J Clin Oncol. 2002;20(14):3095-3105. 2. Nahta R et al. Nat Clin Pract Oncol. 2006;3(5):269-280.
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Importance of HER2 Testing The 2013 revision to the ASCO/CAP guidelines recommends that every case of primary, recurrent, or metastatic breast cancer be evaluated for HER2, ER, and PR status - HER2 testing is the only means for determining eligibility for HER2-directed therapy - HER2 testing should be performed only in labs with demonstrated proficiency in the HER2 assays they perform ASCO/CAP preferentially recommends the use of FDA-approved immunohistochemistry (IHC) and in situ hybridization (ISH) to evaluate HER2 status
Repeat testing is recommended in cases of poor specimen handling, analytical failure, and histopathologic discordance Abbreviations: ASCO, American Society of Clinical Oncology; CAP, College of American Pathologists; FDA, Food and Drug Administration. Reference: Wolff AC et al. J Clin Oncol. 2013;31(31):3997-4013.
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HER2-Targeted Treatment Approaches Selectively target HER2overexpressing cancer cells
Inhibit HER2 function - Extracellular - Intracellular
Abbreviations: AKT, protein kinase B; hsp90, heat shock protein 90; mAb, monoclonal antibody; mTOR, mammalian target of rapamycin; P, phosphorylation site; PI3K, phosphoinositide 3–kinase; TKI, tyrosine-kinase inhibitor. Reference: Montemurro F, Scaltriti M. J Pathol. 2013;232(2):219-229.
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Key Points Patients diagnosed with MBC face a different set of challenges than patients diagnosed with early-stage disease Treatment for MBC focuses on palliative care, symptom management, and extending survival rather than on curative measures HER2-positive MBC is highly aggressive and is associated with reduced 5year survival rates Treatment of HER2-positive MBC with HER2-directed agents at the earliest approved setting may improve overall survival
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