Case Discussion A 37-year-old woman presented with a clinical T2 breast lesion (~3.5 cm by imaging). Biopsy revealed HER2-positive, ER/PR-poor breast.

Case Discussion A 37-year-old woman presented with a clinical T2 breast lesion (~3.5 cm by imaging). Biopsy revealed HER2-positive, ER/PR-poor breast cancer (BC). Patient received TCHP.

CREATE-X: Phase III Trial of Adjuvant Capecitabine
Eligibility HER2-negative, Stage I- IIIB BC Residual invasive BC after neoadjuvant chemotherapy No prior treatment with oral 5-FU Capecitabine (n = 440) R Control (n = 445) Outcome Capecitabine (n = 440) Control (n = 445) HR p-value Five-year DFS 74.1% 67.7% 0.70 Five-year OS 89.2% 83.9% 0.60 <0.01 Toi M et al. San Antonio Breast Cancer Symposium 2015;Abstract S1-07.

Should the patient receive hormone-directed therapy or chemotherapy?
Case Discussion A 58-year-old woman with T1c N1 Stage II BC (single node with microscopic involvement) and no comorbidities Biopsy revealed HER2-negative, ER/PR-positive disease Should the patient receive hormone-directed therapy or chemotherapy?

Case Discussion A 58-year-old woman with T1c N1 Stage II BC (single node with microscopic involvement) and no comorbidities Biopsy revealed HER2-negative, ER/PR-positive disease 21-gene assay Recurrence Score® is 12

Distant metastasis-free survival at 5 years
MINDACT Trial: 70-Gene Signature Test (MammaPrint®) as an Aid to Treatment Decisions in Early-Stage BC Distant metastasis-free survival at 5 years Low clinical and genomic risk (n = 2,745) 97.6% High clinical, low genomic risk (n = 1,550) 95.1% Low clinical, high genomic risk (n = 592) 94.8% High clinical and genomic risk (n = 1,806) 90.6% Cardoso F et al. N Engl J Med 2016;375(8):

Perspective on the Results of the MINDACT Trial
“I think it is Level 1 evidence. This is a big trial. It’s got a lot of patients in it. I think their prognostic information is valid. I think, in order to replicate what was done in this trial, you have to use Adjuvant! Online… Adjuvant! Online is not available. So making the case that you can use other things to arrive at the same information, I think maybe that’s true, maybe it’s not.” William J Gradishar, MD

Second Opinion: Case Discussion
A man in his late thirties was diagnosed with locally advanced strongly HER2-positive, ER-positive BC Patient had palpable nodes and a palpable mass Patient underwent surgery and received trastuzumab for 1 y  endocrine therapy but experienced disease progression

A man in his late thirties was diagnosed with locally advanced strongly HER2-positive, ER-positive BC Patient had palpable nodes and a palpable mass Patient underwent surgery and received trastuzumab for 1 y  endocrine therapy but experienced disease progression Subsequent bone biopsy revealed ER-positive, HER2-poor disease Patient is currently receiving T-DM1

Approach to Fertility in Young Patients with BC
“We do know that in those that are going to get chemotherapy, that their fertility can be impacted — some evidence that you can use drugs like GnRH agonists that can help maintain ovarian function after the chemotherapy is done, increasing the chances of fertility. Those are all things that have to be considered before you start systemic therapy. We also know that now that we’re talking about longer durations of therapy with endocrine therapy, that you may close the window on a woman if you say, ‘You have to complete all your therapy before you can consider getting pregnant,’ particularly if we’re talking about 5 and 10 years in a 30-year-old woman. So as a practice, it’s not uncommon for us to accept that a break is acceptable, if they want to try and get pregnant.” William J Gradishar, MD

Select Ongoing Trials for AR-Positive Triple-Negative BC (TNBC)
Trial name Phase N Setting Study arms Arbre (NCT ) II 60 Metastatic, ≥1 prior regimens Bicalutamide Physician’s choice of therapy ARB (NCT ) 235 Preoperative, primary Cohort I: Exemestane +/-Enzalutamide Cohort II: Enzalutamide SYSUCC-007 (NCT ) III 262 First line, metastatic Physician’s choice of chemotherapy Accessed February 2017.

Utility of Adjuvant Bisphosphonates for Early BC
“A meta-analysis has suggested that, if there is a benefit, say, from bisphosphonates, the argument is most compelling in patients who have an estrogen-poor environment, such as postmenopausal women rather than premenopausal women. The guidelines haven’t really spoken out on this definitively… But there is some clear anticancer effect of these agents that can be demonstrated preclinically. And there’s also data that we’ll see with denosumab, the RANK ligand inhibitor, in this same setting. But right now, the most data we have is from a meta-analysis with the bisphosphonates suggesting that there might be a reduction in the odds of recurrence in postmenopausal women in an estrogen-deprived environment.” William J Gradishar, MD

Case Discussion A 42-year-old woman diagnosed with a right side IDC
Preoperatively, she had 1 focus of disease in the breast Patient elected to undergo mastectomy and sentinel lymph node biopsy Pathology showed multifocal, moderately differentiated, strongly ER/PR-positive, HER2- negative T1b disease 3 sentinel lymph nodes were negative The 21-gene Recurrence Score is 19

Will she benefit from adjuvant chemotherapy?
Case Discussion A 42-year-old woman diagnosed with a right side IDC Preoperatively, she had 1 focus of disease in the breast Patient elected to undergo mastectomy and sentinel lymph node biopsy Pathology showed multifocal, moderately differentiated, strongly ER/PR-positive, HER2- negative T1b disease 3 sentinel lymph nodes were negative The 21-gene Recurrence Score is 19 Will she benefit from adjuvant chemotherapy?

Case Discussion A 36-year-old woman newly diagnosed with a clinical T2N0 triple-negative IDC in the left breast She did not carry an inherited predisposition to TNBC She received neoadjuvant cisplatin on a clinical trial investigating whether pCR rates after treatment correlate with the homologous recombination deficiency (HRD) assay for women with TNBC

Utility of the HRD Assay in the Management of TNBC
“The known hereditary BRCA mutation tumors do tend to have deficiency of DNA repair mechanisms, and HRD is one of those repair mechanisms. So if somebody has a germline BRCA1 mutation, then their tumor will be HRD deficient and potentially more susceptible to agents that cause DNA damage. But we also know that there are some sporadic triple-negative breast cancers that also have HRD deficiency. And so the idea is, can we use an assay to identify those women, because they may also be good candidates for these agents.” Tari King, MD

Patient was motivated to try breast-conservation therapy
Case Discussion A 36-year-old woman newly diagnosed with a clinical T2N0 triple-negative IDC in the left breast She did not carry an inherited predisposition to TNBC She received neoadjuvant cisplatin on a clinical trial investigating whether pCR rates after treatment correlate with the homologous recombination deficiency (HRD) assay for women with TNBC Patient was motivated to try breast-conservation therapy

ALTERNATE Phase III Neoadjuvant Trial
Anastrozole Eligibility (n = 2,820) Postmenopausal women with ER- positive, HER2- negative invasive BC cT2-4 N0-3 M0 BC R Fulvestrant Anastrozole + fulvestrant Suman VJ et al. Chin Clin Oncol 2015;4(3):34; NCT

Benefits and Limitations of the DCIS Score
The DCIS Score is very similar to the 21-gene Recurrence Score: The genes aren’t exactly the same, but certainly the concept is the same. The DCIS Score separates women into low, intermediate or high risk for in-breast recurrence, not for distant recurrence. The DCIS Score provides us with prognostic information. It may be a useful tool for counseling women as to their risk of recurrence. The limitation is that the DCIS Score does not tell us anything predictive about response to therapy. Tari King, MD

Meta-analysis of Margin Width and Ipsilateral Breast Tumor Recurrence (IBTR)
A multidisciplinary consensus panel’s systematic review of 20 studies, including 7,883 patients, and other published literature provide the evidence base for consensus. Conclusions: Use of a 2-mm margin as the standard for an adequate margin in DCIS treated with whole-breast irradiation is associated with lower rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes and decrease healthcare costs. Clinical judgment should be used in determining the need for further surgery in patients with negative margins narrower than 2 mm. Morrow M et al. Pract Radiat Oncol 2016;6(5):

ECOG-ACRIN E5194 Trial for Women with DCIS of the Breast Treated with Lumpectomy without Radiation Therapy Outcome Cohort 1 (n = 561) Cohort 2 (n = 104) Five-year rate of developing an IBE 6.0% 15.0% Five-year rate of developing an invasive IBE 2.7% 5.3% Ten-year rate of developing an IBE 12.5% 24.6% Ten-year rate of developing an invasive IBE 6.4% 13.4% IBE = ipsilateral breast event Cohort 1: Low or intermediate grade DCIS, tumor size ≤2.5 cm Cohort 2: High grade DCIS, tumor size ≤1 cm Solin LJ et al. J Clin Oncol 2015;33(33):

Case Discussion A 47-year-old premenopausal woman with Stage IIB (pT2N1M0) ductal carcinoma of the left breast, s/p wide excision 1 of 3 positive sentinel nodes with a 5-mm macrometastasis The primary tumor was 2.1 cm in size (intermediate grade) Biopsy revealed strongly ER/PR-positive, HER2-negative disease 21-gene Recurrence Score is 13 Patient wishes to avoid chemotherapy and received endocrine therapy alone

Ongoing TAILORx Phase III Trial Design
Key eligibility criteria Node-negative BC ER-pos, HER2-neg T1c-T2, all grade (high-risk T1b) Preregister 21-gene assay Estimated accrual (n = 11,248) Register Specimen banking Secondary study group RS < 11 Primary study group RS 11-25 Secondary study group 2 RS > 25 ARM A Hormonal therapy alone Randomization Stratification factors: Tumor size, menopausal status, planned chemo, planned radiation ARM D Chemotherapy + hormonal therapy ARM B Hormonal therapy alone ARM C Chemotherapy + hormonal therapy Sparano JA, Paik S. J Clin Oncol 2008;26(5):721-8; NCT

Ongoing RxPONDER Phase III Trial Design
Estimated accrual: 10,000 Eligibility HR-positive, HER2- negative invasive BC 1-3 positive nodes 21-gene Recurrence Score ≤25 Endocrine therapy only R Chemotherapy + endocrine therapy NCT

PlanB Phase III Trial Design
Eligibility (n = 3,198) HER2-neg primary BC after adequate surgical treatment Age ≤75 years M0 pN+ pN0 high risk RANDOMI ZAT ION HR- Doc + C x 6 RE CURRENCE SCORE 0-3 LN and RS >11 or ≥4 LN E + C x 4  Doc x 4 HR+ 0-3 LN and RS ≤11 Endocrine therapy LN = lymph node; RS = Recurrence Score; Doc = docetaxel; E = epirubicin; C = cyclophosphamide Gluz O et al. J Clin Oncol 2016;34(20):

PlanB Trial Results: Five-Year Disease-Free Survival (DFS)
Endocrine therapy alone Chemotherapy RS ≤11 RS 12-25 RS >25 Five-year DFS 94% 84% Gluz O et al. Proc EBCC 2016;Abstract 8LBA.

MINDACT Trial: Genomic Classification
The MINDACT population: Chemotherapy (CT) assignment according to a “clinical” vs a “genomic” strategy Whole population N = 6,693 41% 27% Discordant N = 2,745  Clinical Low/  genomic Low N = 1,806  Clinical High/  genomic High 9% 23% N = 592  Clinical Low/  genomic High N = 1,550  Clinical High/  genomic Low  “Clinical” strategy CT to 1, ,806 = 3,356 pts = 50%  “Genomic” strategy CT to ,806 = 2,398 pts = 36% 14% reduction 46% reduction in chemotherapy use if applied only to the 50% of patients at clinical high risk Piccart M et al. Proc AACR 2016;Abstract CT039.

Clinical Outcome of the MINDACT Trial at 5 Years of Follow-Up
Risk group clinical High/genomic Low N = 1,550 Median age = 55 y T size > 2 cm 58% Node-positive 48% Luminal 90% HER2-pos 8% Triple-neg 1% Grade 3 29% R No chemotherapy compliance = 89% Chemotherapy compliance = 85% Received endocrine therapy: 94% Received trastuzumab: 5% Piccart M et al. Proc AACR 2016;Abstract CT039.

Clinical Outcome in the Clinical High/Genomic Low Discordant Risk Group of the MINDACT Trial: Five-Year Distant Metastasis-Free Survival (DMFS) No chemotherapy (n = 636) Chemotherapy (n = 592) HR p-value Five-year DMFS 94.8% 96.7% 0.65 0.106 Piccart M et al. Proc AACR 2016;Abstract CT039.

First Outcome Data from 930 Patients with BC with >5 Years Median Follow-Up for Whom Treatment Decisions in Clinical Practice Incorporated the 21-Gene Recurrence Score (RS) Assay Patients who received chemotherapy Five-year risk RS <18 1% RS 18-30 28% RS ≥31 85% Distant Recurrence by RS Category RS group Five-year risk p-value High (n = 89) 4.0% 0.004 Intermediate ( n= 362) 2.3% Low (n = 479) 0.5% Stemmer S et al. Proc ESMO 2015;Abstract 1963; SABCS 2015;Abstract P

Validation of the 21-Gene Expression Assay in BC
Eligibility (n = 10,253) HR-positive, HER2-negative, axillary node-negative BC Tumor size: 1.1 to 5.0 cm or 0.6 to 1.0 cm and intermediate/high tumor grade Eligible for consideration of adjuvant chemotherapy on the basis of clinicopathologic features Patients with RS 0-10 were assigned to receive endocrine therapy only without chemotherapy n = 1,626 Five-year rate of invasive disease-free survival 93.8% Five-year rate of freedom from BC recurrence at a distant site 99.3% Five-year rate of overall survival 98.0% Sparano JA et al. N Engl J Med 2015;373(21):

Genomic Health SEER Database (N = 38,568)
RS <18 RS 18-30 RS ≥31 Five-year BC-specific mortality (BCSM) 0.4% 1.4% 4.4% Five-Year BCSM by Recurrence Score Group and Known Chemotherapy Treatment RS <18 RS 18-30 RS ≥31 N BCSM All patients 21,023 0.4% 14,494 1.4% 3,051 4.4% Known chemotherapy use 54% 38% 8% No/unknown 19,554 9,570 936 6.0% Yes 1,469 0.7% 4,924 2,115 3.6% Shak S et al. San Antonio Breast Cancer Symposium 2015;Abstract P

Case Discussion A 52-year-old premenopausal woman with a history of lobular carcinoma in situ (LCIS) presented with a palpable 3-cm mass in the upper-outer right breast No clinical axillary adenopathy at time of diagnosis She opted for breast-conservation therapy Biopsy revealed ER/PR-positive, HER2-negative, Ki-67-low BC; 3 sentinel nodes were free of cancer 21-gene Recurrence Score is 12. Hence, she received endocrine therapy alone.

Decision-Making Process for Performing the 21-Gene Assay
First we discuss with the patient Particularly for patients with 1 to 3 positive nodes I never order the 21-gene test without either a telephone conversation or conference discussion with a medical oncology colleague This is because it would be a waste to order the test if the information obtained would not be considered valuable by medical oncologists Seema A Khan, MD, MPH

Case Discussion A 52-year-old premenopausal woman with a history of LCIS presented with a palpable 3-cm mass in the upper-outer right breast No clinical axillary adenopathy at time of diagnosis She opted for breast-conservation therapy Biopsy revealed ER/PR-positive, HER2-negative, KI67-low BC; 3 sentinel nodes were free of cancer 21-gene Recurrence Score is 12. Hence, she received endocrine therapy alone

Phase II ACOSOG-Z1071 Trial of Sentinel Lymph Node (SLN) Surgery and Axillary Lymph Node Dissection (ALND) Eligibility (n = 756): Women with clinical Stage T0-4 N1-2 M0 invasive BC who received neoadjuvant chemotherapy Of 663 evaluable patients with cN1 disease: No SLN cancer was identified in 46 patients (7.1%) A single SLN was excised in 78 patients (12.0%) For 525 patients with ≥2 SLNs removed, the pathologic complete nodal response rate was 41.0% In 39 patients, cancer was not identified in the SLNs but was found in lymph nodes obtained with ALND, resulting in a false-negative rate of 12.6%. Boughey JC et al. JAMA 2013;310(14):

Trial Evaluating Locoregional Control of Metastatic BC (MBC) (Tata Memorial Centre, Mumbai, India)
Stratified by site of metastasis (visceral, bone, both), number of metastases (≤3 or >3), ER/PR status (positive or negative) Locoregional treatment (n = 173) MBC at first presentation; planned anthracycline-based treatment (N = 350) Anthracyclines ± taxanes (CR/PR) R No locoregional treatment (n = 177) Locoregional therapy (n = 177) No locoregional therapy (n = 173) HR p-value Median OS 19.2 mo 20.5 mo 1.04 0.79 Badwe R et al. SABCS 2013;Abstract S2-02; Lancet Oncol 2015;16(13):

Protocol MF07-01 (Turkish Trial)
Stage IV BC at presentation (N = 350) R Systemic therapy Local therapy to breast +/- axilla Local therapy for local progression Systemic therapy Locoregional therapy (n = 138) No locoregional therapy (n = 136) HR p-value Median OS 46 mo 37 mo 0.66 0.005 Soran A et al. Proc ASCO 2016;Abstract 1005.

A 49-year-old woman presented with a right breast mass: ER/PR-negative, HER2-positive BC She had a solitary liver lesion, biopsy-proven to be metastatic disease She received 6 cycles of paclitaxel in combination with trastuzumab/pertuzumab with a clinical response Should she undergo breast surgery?

A 49-year-old woman presented with a right breast mass: ER/PR-negative, HER2-positive BC She had a solitary liver lesion, biopsy-proven to be metastatic disease She received 6 cycles of paclitaxel in combination with trastuzumab/pertuzumab with a clinical response What type of surgical therapy to the breast should she undergo?

A 59-year-old woman presented with a 2-cm ER-positive, HER2-negative breast tumor in 2011 Biopsy revealed sentinel node-negative disease Patient underwent lumpectomy, adjuvant chemotherapy  radiation therapy  adjuvant letrozole After 4 years on letrozole, she experiences local recurrence in the breast What is the role of sentinel node biopsy in local recurrence?

Decision-Making about “Pseudo-adjuvant” Therapy for BC Recurrence
I think one needs to make the decision about what you call “pseudo-adjuvant” therapy based on the characteristics of the tumor and the recurrence. I’m not sure that nodal information will add a lot, so I don’t see the value of doing an internal mammary node biopsy, which can be quite morbid, or going to the other axilla or to the supraclavicular region, which a second sentinel node might mean, if I’m not convinced that in fact this nodal information really should change our treatment. Seema A Khan, MD, MPH

A 59-year-old woman presented with a 2-cm ER-positive, HER2-negative breast tumor in 2011 Biopsy revealed sentinel node-negative disease Patient underwent lumpectomy, adjuvant chemotherapy  radiation therapy  adjuvant letrozole After 4 years on letrozole, she experiences local recurrence in the breast What are the therapeutic options?

CALOR: Phase III Trial of Adjuvant Chemotherapy
Eligibility (n = 162) First ipsilateral local and/or regional recurrence after surgery Complete gross excision of recurrence No evidence of supraclavicular lymph nodes or distant metastases No chemotherapy (n = 77) R Adjuvant chemotherapy (≥3 courses) (n = 85) Five-year DFS Chemotherapy No chemotherapy HR p-value All patients (n = 85, 77) 69% 57% 0.59 0.046 ER-positive (n = 56, 48) 70% 0.94 0.87 ER-negative (n = 29, 29) 67% 35% 0.32 0.007 Aebi S et al. Lancet Oncol 2014;15(2):156-63; SABCS 2012;Abstract S3-2.

Case Discussion A 37-year-old woman presented with a clinical T2 breast lesion (~3.5 cm by imaging). Biopsy revealed HER2-positive, ER/PR-poor breast.

Similar presentations

Presentation on theme: "Case Discussion A 37-year-old woman presented with a clinical T2 breast lesion (~3.5 cm by imaging). Biopsy revealed HER2-positive, ER/PR-poor breast."— Presentation transcript:

Similar presentations

About project

Feedback

Log in

Auth with social network:

Case Discussion A 37-year-old woman presented with a clinical T2 breast lesion (~3.5 cm by imaging). Biopsy revealed HER2-positive, ER/PR-poor breast.

Similar presentations

Presentation on theme: "Case Discussion A 37-year-old woman presented with a clinical T2 breast lesion (~3.5 cm by imaging). Biopsy revealed HER2-positive, ER/PR-poor breast."— Presentation transcript:

Similar presentations

About project

Feedback