Triple Negative Breast Cancer. Disclosures. Objectives 5/1/2015. Deborah K Walker, DNP, CRNP, AOCN Assistant Professor/Nurse Practitioner

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1 Triple Negative Breast Cancer Deborah K Walker, DNP, CRNP, AOCN Assistant Professor/Nurse Practitioner Disclosures I have nothing to disclose in relation to the TNBC presentation. Objectives Improve understanding triple negative breast cancer (TNBC) Enhance understanding of estrogen receptors, progesterone receptors and human epidermal growth factor receptor 2 (HER2) specific to patients with TNBC Discuss potential new strategies for treatment of TNBC and assess their practical benefits and limitations to inform decision making 1

2 Definition Triple Negative Breast Cancer (TNBC) Describes breast cancer cells that do not have estrogen receptors, progesterone receptors, or large amounts of HER2/neu protein. Also called ER negative PR negative HER2/neu negative breast cancer. (NCI, 2015) Overview About 10 20% ~200,000 cases each yr Significantly more aggressive than other subtype tumors Most are basal like cells look like the basal cells that line the breast ducts Basal like cancers tend to overexpress or make to much of a certain gene that encourages cancer growth NOT ALL basal like cancers are TNBC (ABOUT 70 90%) Who gets its? Younger people. more likely to occur before age 40 or 50, versus age 60 or older, which is more typical for other breast cancer types. African American and Hispanic women. most commonly affects African American women, followed by Hispanic women. Asian women and non Hispanic white women are less likely to develop this type of cancer. One study found that black women were 3 times more likely to develop triple negative breast cancer than white women. People with a BRCA1 mutation. When people with an inherited BRCA1 mutation develop breast cancer, especially before age 50, it is usually found to be triple negative. 2

3 Risk Factors Clinical Presentation Aggressive with rapid growth More likely to be diagnosed clinically rather than by MMG (than ER+ BC) Or as interval cancers between MMG Pathophysiology Breast cancer is divided into subgroups and distinguished by tumor appearance based on histologic classification system Tumor size, LN involvement, distant metastasis And other characteristics: stage, histopathology, grade, receptor status TNBC has the distinct pathologic features (ER /PR /HER2 ) that: Tends to be more aggressive than other types of breast cancer Tends to be higher grade than other types of breast cancer. Common histology is infiltrating ductal carcinoma Usually is a cell type called basal like. Aggressive metastasis Poor prognosis Limits treatment options 3

4 Pathophysiology Triple negative breast cancers have a relapse pattern that is very different from hormone positive breast cancers: the risk of relapse is much higher for the first 1 3 years but drops sharply and substantially below that of hormone positive breast cancers after that. This relapse pattern has been recognized for all types of triple negative cancers for which sufficient data exists although the absolute relapse and survival rates differ across subtypes Increased mortality rate first 5 years Rapid progression from distant recurrence to death Molecular Classification TNBC phenotype mostly basal like molecular subtype Basal BC has a genomic expression of basal cluster a unique cluster of genes that includes EGFR, basal cytokeratins 5/6, c Kit, the proliferation cluster and low expression of the hormone receptor and HER2 related genes Separate subtypes of TNBC have been characterized by gene expression (next slide) Gene expression analysis has also revealed tumor suppressor gene p53 as well as others in TNBC, which may have implications for chemotherapy sensitivity Gene Expression Profiling Classification SUBGROUPS Basal like 1 Basal like 2 Immunomodulatory Mesenchymal like Mesenchymal stem like Luminal AR Basal like like expression profile characteristics Low ER (and associated genes) expression Low HER2 expression Usually triple negative High basal cluster Basal cytokeratins EGFR c kit Others Very proliferative Often p53 mutant Evidence of genomic instability 4

5 Diagnosis and Staging Diagnosis Hormone receptor negativity as less than 1 percent staining of tumor cells by immunohistochemistry (IHC) We define TNBC as hormone receptor negative and HER2negative (IHC 0 to 1+ or fluorescence insitu hybridization [FISH] non amplified). Staging Is identical across BC types using TNM method Prognostic Factors Prognostic Factors The menopausal status of the patient. The stage of the disease. The grade of the primary tumor. The estrogen receptor (ER) and progesterone receptor (PR) status of the tumor. Human epidermal growth factor type 2 receptor (HER2/neu) overexpression and/or amplification. The histologic type. Breast cancer is classified into a variety of histologic types, some of which have prognostic importance. For example, favorable histologic types include mucinous, medullary, and tubular carcinomas. Prognostic Factors Prognostic Factors The use of molecular profiling in breast cancer includes the following: ER and PR status testing. HER2/neu receptor status testing. Gene profile testing by microarray assay or reverse transcription polymerase chain reaction (e.g., MammaPrint, Oncotype DX). On the basis of these results, breast cancer is classified as: Hormone receptor positive. HER2 positive. Triple negative (ER, PR, and Her2/neu negative). 5

6 TREATMENT APPROACH Adjuvant therapy for early breast cancer (90% are early at diagnosis). Lisa A. Carey The Oncologist 2011;16: by AlphaMed Press Treatment options Surgery Breast conserving followed by radiation Mastectomy for extensive multifocal disease there is no standard recommendation that people with triple negative breast cancer should have more treatment. such as mastectomy, if not indicated 6

7 Treatment options Chemotherapy Neoadjuvant vs adjuvant Many patients treated with adjuvant anthracycline, taxane, and cyclophosphamide Platinums clinical role less clear but promising in BRCA1+ Ixabepilone evidence of activity, but difficult to assess Treatment options Targeted therapies clinical trials PARP inhibitors are showing promise. VEGF inhibitors Avastin EGFR inhibitors targeted therapies in combination (expressed in 50% of TNBC) mtor inhibitors (mixed results) PI3 Kinase inhibitors Jak2/Stat3 pathway Treatment options Radiation therapy next presentation 7

8 Clinical Management Assist in early detection Teach about breast selfawareness Clinical Management Patient education on risk factors Factors That Decrease Your Risk Being older when you first had your menstrual period. Starting menopause at an earlier age. Giving birth to more children, being younger at the birth of your first child, and breastfeeding your children. Getting regular exercise. Maintaining ahealthy weight. Factors That Increase Your Risk Long term use of hormone replacement therapy. Personal history of breast cancer or non cancerous breast diseases. Family history of breast cancer (on either your mother s or father s side of the family). Treatment with radiation therapy to the breast/chest. Exposure to diethylstilbestrol (DES) (for example, if you took DES during pregnancy or your mother took DES during her pregnancy with you). Dense breasts by mammogram. Drinking alcohol. Night shift work. Clinical Management Psychosocial issues depression, anxiety, low self esteem, poor QOL These patients typically have increased emotional distress Dealing with uncertainty, fears of recurrence (1 st 5 years) 8

9 Myths Women with TNBC can have same treatment as all other women with breast cancer No no hormones, MAB TNBC are always hard to treat Really depends on tumor size, LN involvement, as much as it does on TN status Only African American women get TNBC 2 3 times more likely to have TNBC than white women Resources Living Beyond Breast Cancer National Breast Cancer Foundation, Inc. negative breast cancer National Cancer Institute Susan G Komen Triple Negative Breast Cancer Foundation Search of ClinicalTrials.Gov Using Term Triple Negative Breast Cancer : Novel Agents Conclusions TNBC is generally initially chemosensitive but aggressive with a characteristic relapse pattern TNBC and basal like breast cancer overlap but are not identical Sporadic TNBC share a variety of characteristics with BRCA deficient tumors Impaired DNA repair Genomic disarray High grade disease Treatment strategies for TNBC cancers appear promising based on biologic subgroups Enrollment on clinical trial recommended 9

10 LATE BREAKING NEWS Latest News Study predicts breast cancer incidence will grow by 50% from 2011 to 2030 Denser breasts may put black women at greater risk of breast cancer New drug WEDNESDAY, Feb. 4, 2015 A new drug to treat postmenopausal women with advanced breast cancer has been approved by the U.S. Food and Drug Administration. Pfizer's Ibrance (palbociclib) inhibits molecules that play a role in the growth of cancer cells. It is intended for postmenopausal women with estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer who have not yet received endocrine based therapy 10

11 Controversial Draft recommendations from the U.S. Preventive Services Task Force call for regular mammogram screenings every two years for women 50 to 74 years old. The guidelines call for women in their 40s to discuss whether they need screening with their health care providers, making decisions about mammography based on individual risk factors and health history as well as the potential benefits and harms of screening. The task force found insufficient evidence to recommend for or against 3D mammography as well as a dearth of evidence regarding other types of imaging for women with dense breasts. Questions?? 11