Results of a novel neoadjuvant chemotherapy (NAC) regimen for breast cancer.

e11610 Background: Achieving a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) has been associated with improved disease free survival (DFS) and overall survival (OS). The Residual Cancer Burden Score (RCB) method is a useful tool that predicts DFS and OS after NAC. We present the results of pts with either triple negative or HER2 positive breast cancer treated with a novel NAC. Methods: 34 pts with localized breast cancer >1 cm with HER2+ (N=19) or triple negative breast cancer (TNBC) (N=15) were treated with this novel regimen consisting first of TEC (docetaxel 75 mg/m2, epirubicin 80 mg/m2, and cyclophosphamide 500 mg/m2) + PEG Filgrastim x 4 cycles. Following the 4th course, TNBC patients received 4 additional TEC cycles if they achieved CR by MRI, or were switched to a non cross-resistant regimen (vinorelbine, bevacizumab, capecitabine) if they had < CR. HER2+ pts received TEC x4 followed by docetaxel + trastuzumab x 4. RCB score was used to measure pathologic response. Pretreament PET scan was done and repeated after course 1 in order to correlate with RCB. Results: Median age was 56 (58 for Her2+ and 49 for TNBC). RCB= 0 (pCR) was achieved in 76%, while only 1 responded poorly (RCB=3). There was no significant difference in the pCR rate between Her2+ and TNBC patients (74% vs 80% respectively), but there was a difference in the rate of pCR without DCIS and invasive cancer between these two (see table, p=0.034). Pts with SUV drop > 5% after 1st TEC had 84% pCR while none with < 5% achieved pCR (p=0.001). Comparison of our results with other NAC regimens reported in the literature is summarized in the table below. Conclusions: This novel chemotherapy approach results in a high pCR rate and RCB 0-1, which have been associated with improved clinical outcomes. Early PET can predict pCR. Although sample size is modest, results are encouraging and deserve further evaluation. Clinical trial information: NCT 00830544. [Table: see text]

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Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype

Journal of Clinical Oncology ◽

10.1200/jco.2015.63.1010 ◽

2017 ◽

Vol 35 (10) ◽

pp. 1049-1060 ◽

Cited By ~ 175

Author(s):

W. Fraser Symmans ◽

Caimiao Wei ◽

Rebekah Gould ◽

Xian Yu ◽

Ya Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Validation Cohort ◽

Residual Disease ◽

Pathologic Complete Response ◽

Complete Response ◽

Her2 Positive ◽

Free Survival ◽

Residual Cancer Burden

Purpose To determine the long-term prognosis in each phenotypic subset of breast cancer related to residual cancer burden (RCB) after neoadjuvant chemotherapy alone, or with concurrent human epidermal growth factor receptor 2 (HER2)–targeted treatment. Methods We conducted a pathologic review to measure the continuous RCB index (wherein pathologic complete response has RCB = 0; residual disease is categorized into three predefined classes of RCB index [RCB-I, RCB-II, and RCB-III]), and yp-stage of residual disease. Patients were prospectively observed for survival. Three patient cohorts received paclitaxel (T) followed by fluorouracil, doxorubicin, and cyclophosphamide (T/FAC): original development cohort (T/FAC-1), validation cohort (T/FAC-2), and independent validation cohort (T/FAC-3). Another validation cohort received FAC chemotherapy only, and a fifth cohort received concurrent trastuzumab (H) with sequential paclitaxel and fluorouracil, epirubicin, and cyclophosphamide (FEC; H+T/FEC). Phenotypic subsets were defined by hormone receptor (HR) and HER2 status at diagnosis, classified as HR-positive/HER2-negative, HER2-positive (HR-negative/HER2-positive or HR-positive/HER2-positive), or triple receptor–negative. Relapse-free survival estimates were determined from Kaplan-Meier analysis and compared using the log-rank test. Results Five cohorts (T/FAC-1 [n = 219], T/FAC-2 [n = 262], T/FAC-3 [n = 342], FAC [n = 132], and H+T/FEC [n = 203]) had median event-free follow-up of 13.5, 9.1, 6.8, 16.4, and 7.1 years, respectively. Continuous RCB index was prognostic within each phenotypic subset, independent of other clinical-pathologic variables. RCB classes stratified prognostic risk overall, within each phenotypic subset, and within yp-stage categories. Estimates of 10-year relapse-free survival rates in the four RCB classes (pathologic complete response, RCB-I, RCB-II, and RCB-III) were 86%, 81%, 55%, and 23% for triple receptor–negative; 83%, 97%, 74%, and 52% for HR-positive/HER2-negative in the combined T/FAC cohorts; and 95%, 77%, 47%, and 21% in the H+T/FEC cohort. Conclusion RCB was prognostic for long-term survival after neoadjuvant chemotherapy in all three phenotypic subsets of breast cancer. Our institutional findings should be externally validated.

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Abstract P6-06-20: Predictive factors for pathologic complete response and disease-free survival after neoadjuvant chemotherapy with trastuzumab: A multicenter retrospective observational study in patients with HER2-positive primary breast cancer (JBCRG-C03 study)

10.1158/0008-5472.sabcs13-p6-06-20 ◽

2013 ◽

Author(s):

M Takada ◽

H Ishiguro ◽

S Nagai ◽

S Ohtani ◽

H Kawabata ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Observational Study ◽

Predictive Factors ◽

Pathologic Complete Response ◽

Disease Free Survival ◽

Complete Response ◽

Her2 Positive ◽

Free Survival ◽

Disease Free

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Pathologic Complete Response Predicts Recurrence-Free Survival More Effectively by Cancer Subset: Results From the I-SPY 1 TRIAL—CALGB 150007/150012, ACRIN 6657

Journal of Clinical Oncology ◽

10.1200/jco.2011.39.2779 ◽

2012 ◽

Vol 30 (26) ◽

pp. 3242-3249 ◽

Cited By ~ 265

Author(s):

Laura J. Esserman ◽

Donald A. Berry ◽

Angela DeMichele ◽

Lisa Carey ◽

Sarah E. Davis ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Tumor Biology ◽

Pathologic Complete Response ◽

Complete Response ◽

High Risk Group ◽

Hazard Ratio ◽

Recurrence Free Survival ◽

Her2 Positive ◽

Free Survival

PurposeNeoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting recurrence-free survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers.Patients and MethodsEligible patients had tumors ≥ 3 cm and received neoadjuvant chemotherapy. We determined associations between pathologic complete response (pCR; defined as the absence of invasive cancer in breast and nodes) and RFS, overall and within receptor subsets.ResultsIn 221 evaluable patients (median tumor size, 6.0 cm; median age, 49 years; 91% classified as poor risk on the basis of the 70-gene prognosis profile), 41% were hormone receptor (HR) negative, and 31% were human epidermal growth factor receptor 2 (HER2) positive. For 190 patients treated without neoadjuvant trastuzumab, pCR was highest for HR-negative/HER2-positive patients (45%) and lowest for HR-positive/HER2-negative patients (9%). Achieving pCR predicted favorable RFS. For 172 patients treated without trastuzumab, the hazard ratio for RFS of pCR versus no pCR was 0.29 (95% CI, 0.07 to 0.82). pCR was more predictive of RFS by multivariate analysis when subtype was taken into account, and point estimates of hazard ratios within the HR-positive/HER2-negative (hazard ratio, 0.00; 95% CI, 0.00 to 0.93), HR-negative/HER2-negative (hazard ratio, 0.25; 95% CI, 0.04 to 0.97), and HER2-positive (hazard ratio, 0.14; 95% CI, 0.01 to 1.0) subtypes are lower. Ki67 further improved the prediction of pCR within subsets.ConclusionIn this biologically high-risk group, pCR differs by receptor subset. pCR is more highly predictive of RFS within every established receptor subset than overall, demonstrating that the extent of outcome advantage conferred by pCR is specific to tumor biology.

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Efficacy of HER2-targeted therapy for patients with HER2-positive breast cancer according to hormone receptor status.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.26_suppl.97 ◽

2013 ◽

Vol 31 (26_suppl) ◽

pp. 97-97

Author(s):

Takeshi Murata ◽

Maiko Takahashi ◽

Tetsu Hayashida ◽

Hiromitsu Jinno ◽

Yuko Kitagawa

Keyword(s):

Breast Cancer ◽

Targeted Therapy ◽

Hormone Receptor ◽

Response Rate ◽

Disease Free Survival ◽

Complete Response ◽

Her2 Positive ◽

Free Survival ◽

Significant Difference ◽

Disease Free

97 Background: Hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-positive tumors generally cluster within the luminal/HER2 subset; whereas HR-negative/HER2-positive tumors reside in HER2-enriched subset. We investigated whether the efficacy of HER2-targeted therapy for HER2-positive tumors differs by HR status. Methods: Sixty-eight patients with operable breast cancer received trastuzumab plus taxane based therapy before surgery at Keio University Hospital from March 2009 to April 2012. All tumors were HER2-positive by immunohistochemistry (IHC) or fluorescence in situ hybridization. Expressions of ER, PgR, and Ki67 were performed by IHC in core needle biopsy samples at baseline. Pathological complete response (pCR) defined as no invasive residuals in breast. All patients with luminal/HER2 tumors received adjuvant endocrine therapy in addition to adjuvant trastuzumab monothereapy. Results: Sixty-eight patients with HER2-positive tumors were divided into 35 (51.5%) patients with luminal/HER2 tumors and 33(48.5%) patients with HER2-enriched tumors, respectively. There were no significant differences in tumor size, clinical nodal status, nuclear grade, and Ki67 status between the two groups. Clinical complete response rate and objective response rate were similar between the two groups. Patients with luminal/HER2 tumors were significantly younger than patients with HER2-enriched tumors (median age (range): 53 (35-78) vs. 61 (31-72), p=0.041). Compared to patients with luminal/HER2 tumors, patients with HER2-enriched tumors had significantly higher pCR rate (28.6% vs. 69.7%, p=0.002). With 24 months median follow-up, no significant differences were observed between the two groups with respect to disease-free survival. Estimated 2-year disease-free survival for luminal/HER2 and HER2-enriched was 94.3% and 97.0%, respectively (p=1.000). Conclusions: HER2-enriched breast cancer showed significantly higher pCR rate to HER2-targeted therapy compared with luminal/HER2 breast cancer. However, there was no significant difference in disease-free survival between the two groups.

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Effect of Trastuzumab among HER2-Positive Breast Cancer Patients that Achieved Pathologic Complete Response after Neoadjuvant Chemotherapy

Breast Care ◽

10.1159/000495186 ◽

2019 ◽

Vol 14 (6) ◽

pp. 388-393

Author(s):

Xinguang Wang ◽

Yingjian He ◽

Zhaoqing Fan ◽

Tianfeng Wang ◽

Yuntao Xie ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Cancer Patients ◽

Pathologic Complete Response ◽

Complete Response ◽

Breast Cancer Patients ◽

Her2 Positive ◽

Free Survival ◽

Her2 Positive Breast Cancer ◽

Positive Breast Cancer

Background: We sought to investigate the incremental benefit of trastuzumab in patients with HER2-positive breast cancer who achieved a pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT). Methods: The data of HER2-positive invasive breast cancer patients treated with NACT and achieving pCR were obtained from the institutional database. Patients were categorized according to trastuzumab administration. The Kaplan-Meier method and log-rank estimates were used to test the association between trastuzumab administration and survival. Univariate and multivariate Cox regressions were used to obtain hazard ratios. Results: Of 223 patients, 83 (37.2%) were treated with NACT without trastuzumab and 140 (62.8%) were treated with NACT plus trastuzumab for 1 year. After a median follow-up of 67 months, the trastuzumab group showed improved relapse-free survival compared with the no-trastuzumab group (95.7 vs. 87.8%, hazard ratio = 0.31, p = 0.028). No significant difference in distant disease-free survival or overall survival was observed (p = 0.250 and 0.432, respectively). Multivariate analysis identified endocrine therapy and trastuzumab administration to be associated with decreased risk of relapse (p = 0.018 and 0.030, respectively). Conclusion: The administration of trastuzumab should be considered standard treatment for HER2-positive patients who have achieved pCR after NACT alone.

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Cytoplasmic Poly(Adenosine Diphosphate–Ribose) Polymerase Expression Is Predictive and Prognostic in Patients With Breast Cancer Treated With Neoadjuvant Chemotherapy

Journal of Clinical Oncology ◽

10.1200/jco.2010.31.9079 ◽

2011 ◽

Vol 29 (16) ◽

pp. 2150-2157 ◽

Cited By ~ 53

Author(s):

Gunter von Minckwitz ◽

Berit Maria Müller ◽

Sibylle Loibl ◽

Jan Budczies ◽

Claus Hanusch ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Pathologic Complete Response ◽

Disease Free Survival ◽

Adenosine Diphosphate ◽

Complete Response ◽

Cellular Stress Response ◽

Her2 Status ◽

Clinical Activity ◽

Her2 Positive

Purpose Poly(adenosine diphosphate–ribose) polymerase (PARP) plays a key role in DNA repair and cellular stress response. Inhibitors of PARP show promising clinical activity in metastatic, triple-negative or BRCA-mutated breast cancer. Patients and Methods We investigated cytoplasmic PARP (cPARP) and nuclear PARP (nPARP) expression by immunohistochemistry in 638 pretreatment biopsies from patients on the GeparTrio study and evaluated its predictive and prognostic value after neoadjuvant anthracycline/taxane-based chemotherapy. Results cPARP expression was high in 23.7%, intermediate in 50.9%, and negative in 25.4% of tumors. High cPARP expression was significantly correlated with nonlobular histology (P < .001), undifferentiated grade (P < .001), positive nodal status (P = .049), and negative hormone receptor (HR) status (P < .001) but not with human epidermal growth factor receptor 2 (HER2) status. Expression was high in 35.5% of triple-negative tumors, 24.6% of HER2-positive tumors, and 18.0% of HR-positive/HER2-negative tumors (P < .001). Pathologic complete response (pCR) rates were 26.5%, 19.1%, and 8.0% in patients with high, intermediate, or negative expression, respectively (P < .001). This predictive effect was most prominent in HR-positive tumors (P = .035) or HER2-negative tumors (P < .001). High cPARP expression was a negative, but not independent, prognostic factor for disease-free survival (DFS; P = .0025) and overall survival (OS; P = .0022). cPARP expression was highly prognostic in patients without a pCR (DFS, P < .001; OS, P < .001) and in patients with HR-positive tumors (DFS, P < .001; OS, P < .001). No such correlations were found for nPARP expression. Conclusion High cPARP expression correlates with aggressive tumor pattern and predicts high sensitivity to neoadjuvant taxane/anthracycline-based chemotherapy but also unfavorable long-term prognosis. As a potential target for PARP inhibitors, cPARP-positive breast cancer might become a new, clinically relevant entity.

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