https://openworks.mdanderson.org/sumexp23/1056/thumbnail.jp

Muppidi, Natasha S

Teshome, Mediget, MD, MPH, FACS

English

OpenWorks @ MD Anderson

MethodsManagement of small early-stage HER2-positive breast cancer: Trends and OutcomesNatasha Muppidi, BS and Mediget Teshome, MD, MPH, FACS1st Year Medical Student ProgramTable 1: Patient demographicsOverall(N=256)Upfront surgery(N=170)NST(N=86)P valueAge at diagnosis, Years 0.0001Median 57 59 53 Mean (range) 57 59.1 (33-85) 52.9 (28-76)Gender 0.3Female 255 170 (100%) 85 (98.8%)Male 1 0 (0) 1 (1.2%)Race 0.07White 186 130 (76.5%) 56 (65.1%)Others 70 40 (23.5%) 30 (34.9%)Asian 18 9 9Black 26 17 9Declined to            answer 2 1 1Other 23 13 10Unknown 1 0 1Ethnicity 0.04Hispanic or Latino 37 19 (11.2%) 18 (20.9%)Not Hispanic or Latino 216 149 (87.7%) 67 (77.9%)Declined to Answer 3 2 (1.2%) 1 (1.2%)BMI 0.7Median 27.5 28 27Mean (range) 28.5 28.6 (17-63) 28.2 (19-66)Overall(N=256)Upfront surgery(N=170)NST(N=86)P valueLargest Clinical tumor size (cm) <0.0001Median - 1.5 2.5Mean (range) - 1.6 (0.1-3) 2.3 (0.9-3)Clinical T stage <0.0001T1 167 145 (85.3%) 22 (25.6%)T1mic 6 6 0T1a 9 9 0T1b 35 34 1T1c 110 90 20T2 89 25 (14.7%) 64 (74.4%)Tumor palpable <0.0001Yes 140 70 (41.2%) 70 (81.4%)No 113 98 (57.7%) 15 (17.4%)Unknown 3 2 (1.2%) 1 (1.2%)Hormone receptor status 0.2HR+ 198 136 (80%) 62 (72.9%)HR- 57 34 (20%) 23 (27.1%)Grade 0.04G1 9 9 (5.3%) 0 (0%)G2 109 75 (44.1%) 34 (39.5%)G3 86 86 (50.6%) 52 (60.5%)Ki67 (%) <0.0001Median 33 30 40Mean (range) 61.4 33.7 (1-80) 45.9 (7-99)DCIS present <0.0001Yes 206 148 (87.1%) 58 (67.4%)No 50 22 (12.9%) 28 (32.6%)Multi-focal/multicentric 0.09Yes 77 45 (26.5%) 32 (37.2%)No 179 125 (73.5%) 54 (62.8%)Overall(N=256)Upfront surgery(N=170)NST(N=86) P valueBreast surgery 0.4Segmental mastectomy 168 114 (68.3%) 54 (62.8%)Total mastectomy 85 53 (31.7%) 32 (37.2%)ALND 0.7Yes 8 6 (3.5%) 2 (2.3%)No 248 164 (96.5%) 84 (97.7%)Adjuvant radiation 0.4Yes 168 114 (67.5%) 54 (63.5%)No 82 51 (30.2%) 31 (36.5%)Unknown 4 4 (2.4%) 0 (0%)Adjuvant endocrine therapy 0.9Yes 183 122 (71.8%) 61 (70.9%)No 73 48 (28.2%) 25 (29.1%)Margin status 0.01Negative 198 124 (72.9%) 74 (86.1%)Close (< 2 mm) 57 46 (27.1%) 11 (12.8%)Unknown 1 0 (0%) 1 (1.2%)Surgery complications 0.8Yes 29 20 (11.8%) 9 (10.5%)No 226 150 (88.2%) 76 (88.4%)Unknown 1 0 (0%) 1 (1.2%)Overall(N=256)Upfront surgery(N=170)NST(N=86) P valuepcRYes 47 N/A 47 (54.7%)No 39 N/A 39 (45.3%)pT size <0.0001Median 0.90 1.3 0 Mean (range) 0.99 1.3 (0-4.3) 0.6 (0-4.8)SLN positive 0.02Yes 24 21 (12.4%) 3 (3.5%)No 232 149 (87.7%) 83 (96.5%)Number of positive SLN 0.090 231 148 (87.6%) 83 (96.5%)1 21 18 (10.6%) 3 (3.5%)2 3 3 (1.8%) 0 (0%)Max positive SLN size (mm) 0.08Median 0.13 0.2 0.08 Mean (range) 0.26 1.3 (0.02-7%) 0.08 (0.05-0.12%)pN stage 0.1N0 233 150 (89.3%) 83 (96.5%)N1 20 17 (10.0%) 3 (3.5%)N3 1 1 (0.6%) 0 (0%)Table 4: Pathologic tumor characteristics72% 72% 70% 65% 65%38%28% 28% 30% 35% 35%62%0%20%40%60%80%100%120%2015 2016 2017 2018 2019 2020Overall Upfront surgery vs. Neoadjuvant Systemic TherapyUpfront Surgery Neoadjuvant systemic therapy• 256 patients met eligibility criteria• 170 (66.4%) received upfront surgery• 86 (33.6%) received NST• Treatment of cT1-2 (≤3 cm) N0 M0 HER2-positive breast cancer has significantly changed over the past several decades.1 • This is secondary to advancements in HER2 targeted therapies, expanding benefits of neoadjuvant systemic therapy2 and clinical trials such as the APT trial supporting abbreviated systemic therapy regimens.3 • Current treatment strategies include neoadjuvant systemic therapy (NST) to assess treatment response followed by surgery, or upfront surgery to define pathologic stage followed by systemic therapy, with advantages and disadvantages associated with both approaches. • An institutional Breast Surgical Oncology database was reviewed from 2015-2020. • Inclusion criteria:• HER2-positive invasive breast cancer• cT1-2N0M0 (clinical tumor size ≤3 cm)• Received surgery at MD Anderson• Exclusion criteria: • Recurrent breast cancer• Concurrent malignancy• Patient, tumor and treatment characteristics were evaluated and compared for patients who received upfront surgery and NST. • Statistical analysis: Student t test was used to compare the means of continuous variables with equal variances. Wilcoxon rank-sum test was used to compare the medians of continuous variables without equal variances. The Χ2 test or Fisher exact test was used for univariate comparison of categorical variables. Multivariate logistical regression models were used to identify factors that significantly predict upgrade to pathologic tumor size (pT) >3 cm or pN1-3 in the upfront surgery group, and residual disease in the breast or ypN1-3 in the NST group. All P values were 2 tailed, and P £ 0.05 was considered significant. Kaplan-Meier survival curves were calculated, and log-rank tests were used to compare the overall survival, disease specific survival, local-regional recurrence free survival and distant recurrence free survival between treatment groups. • Additionally, an electronic survey assessing recommendations for clinical scenarios in management of early-stage HER2-positive breast cancer was sent to MD Anderson medical and surgical oncologists. N=46N=54 N=43 N=46 N=46 N=21Study Objectives• To evaluate the management of small early-stage HER2-positive breast cancer including pathologic, clinical, and oncologic outcomes.• To evaluate trends in management over time and current practice.ConclusionReferencesOncologic Outcomes• 10 (3.9%) patients had any recurrence• Local and regional: 1 (0.4%)• Regional and distant: 2 (0.8%)• Local and distant: 3 (1.2%)• Distant only: 4 (1.6%)• 5 (2.0%) patients diedCurrent Practice: Survey ResultsResponse rate was 39.3% overall (34.2% medical oncologists, 45.8% surgical oncologists). Agreement was 100% for treating cT1aN0 patients with upfront surgery, and cT2N0 (3-5 cm) and cT1-2N1 patients with NST. There was near agreement (92%) for treating cT1bN0 patients with upfront surgery. For cT1cN0 patients, 45% of physicians recommended upfront surgery, and for cT2N0 (<3 cm) patients, 71% recommended NST. These findings were similar to the retrospective review.Pathology PredictorsUpfront surgery: Pathologic upgrade• 4 (2.4%) patients had upgrade to pT >3 cm• 18 (10.6%) patients had upgrade to pN1-3• None of the demographic, clinical tumor, or treatment factors significantly predicted upgrade to pT >3 cm or pN1-3. NST: Pathologic response to therapy• 47 (54.6%) patients had a pathologic complete response (pcR)• Older age at diagnosis (OR 1.08, P = 0.004) and HR-positive status (OR 7.07, P = 0.002) were significant predictors of residual disease (breast) or upgrade to ypN1-3. Management Trends• NST rates increased from 28% to 62% (2015-2020)• cT1mic, cT1a and cT1b tumors almost always received upfront surgery compared to 81.8% of cT1c and 28% of cT2 (≤3 cm) tumors.Background ResultsTable 2: Clinical tumor characteristicsFigure 1: Survival by treatment groupsTable 3: Treatment receivedFigure 2: Proportion of patients receiving upfront surgery vs. NST by year, 2015-20201) Zeridman et al. Trends in neoadjuvant chemotherapy versus surgery-first in stage I HER2-positive breast cancer patients in the National Cancer Database (NCDB). Breast Cancer Research and Treatment. 2021; 187:177-852) Von Minckwitz et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019;380(7):617-283) Tolaney et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med. 2015;372(2):134-141.• Majority of cT1-2 (≤3 cm) N0 HER2-positive breast cancer patients received upfront surgery. • Rates of NST increased over time.• Low rates of pathologic upgrade were observed after upfront surgery. • Older age and HR-positive status were predictors of residual disease (breast) and ypN1-3 disease after NST. • No difference in surgical management or oncologic outcomes was observed between the two groups. • Future studies may consider focusing on cT1c patients to assist in guiding oncologists in the management of this population. 

Management of Small Early-stage HER2-positive Breast Cancer: Trends and Outcomes

https://openworks.mdanderson.org/cgi/viewcontent.cgi?article=1056&context=sumexp23

Management of Small Early-stage HER2-positive Breast Cancer: Trends and Outcomes

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