Abstract P5-06-02: Pathologic complete response (pCR) and prognosis following neoadjuvant chemotherapy plus anti-HER2 therapy of HER2-positive early breast cancer (EBC)

e12503 Background: The pathologic complete response (pCR) rate in primary tumor and axillary node after different chemotherapy regimens of neoadjuvant chemotherapy (NAC) in HER2 positive breast cancer (BC) is unknown, the impact of pCR on disease free survival (DFS) and overall survival (OS) is still controversial. Methods: A cohort of 350 HER2 positive BC (296 cytologically proved axillary node metastasis) received NAC with different regimens, antracyclin with taxotere (AT), docetaxel with transtuzumab (DT) and docetaxel with transtuzumab and pertuzumab( DTP) between 2005 and 2016 in a large medical center were analyzed retrospectively. The impact of pCR rates of breast and axillary node on DFS and OS were analyzed. Results: Of 350 women with HER2 positive BC received NAC, median age was 50 years(18~93), median tumor size was 4.3 cm, the pCR rates of breast and axillary node were 16.2% and 28.7% ( P= 0.018) in patients received AT( n= 130) , 47.6% and 66.9% ( P= 0.00028 ) in patients received DT( n= 191) ,65.5% and 77.8% ( P= 0.372 ) in patients received DTP( n= 29), respectively. The 5-year DFS were 79.3% and 66.0% ( p= 0.0023), 5-year OS were 89.5% and 76.6% ( P= 0.0201) in patients with breast pCR and non-pCR, respectively. The 5-year DFS were 75.7% and 58.4% ( P= 0.00037), 5-year OS were 85.7% and 72.6% ( P= 0.0024) in axillary pCR and non-pCR patients, respectively. The 5-year DFS were 79.3% and 75.7% ( P= 0.430), and 5-year OS were 89.5% and 85.7% ( P= 0.695) in breast and axillary pCR, respectively . The 5-year DFS in breast pCR whom received targeted therapy (DT and DTP groups) was significantly better than whom not received targeted therapy (AT groups), 85.3% and 65.0% ( P= 0.039), respectively Conclusions: Higher pCR rate in axillary node than breast was found in this cohort. Either pCR in axillary node or breast was associated with improved DFS and OS, but no difference of DFS and OS between breast and axillary pCR . The 5-year DFS in breast pCR received targeted therapy were significantly better than breast pCR patients received chemotherapy alone.

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Lapatinib, trastuzumab or the combination added to neoadjuvant chemotherapy for breast cancer

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v11i4.27384 ◽

2016 ◽

Vol 11 (4) ◽

pp. 863

Author(s):

Quan Liang ◽

Qiang Fu ◽

Wei Li ◽

Jiacong You ◽

Zhanchao Zhao

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Response Rate ◽

Complete Response Rate ◽

Pathologic Complete Response ◽

Complete Response ◽

Cochrane Library ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

Positive Breast Cancer

<p>The aim of this study was to compare the efficacy and safety of trastuzumab versus the combination of trastuzumab and lapatinib added to neoadjuvant chemotherapy for HER2 positive breast cancer. PubMed, MEDLINE, The Cochrane Library, Web of Science and nearly 5 years of the important international conference on oncology records were searched for randomized clinical trials that compared lapatinib plus trastuzumab and neoadjuvant chemotherapy (NAC) with trastuzumab in combination with NAC and that included pathologic complete response rate as the primary outcome. Finally, 6 clinical randomized controlled trials were included. Meta-analysis shows that pathological complete response rate was significantly increased in trastu-zumab plus lapatinib group than single use trastuzumab group (53.4%, 40.4%, RR = 1.75, 95% CI 1.38 ~ 2.23, p<0.001). In conclusion, the combination of trastuzumab and lapatinib added to neoadjuvant chemotherapy in HER2 positive breast cancer is more effective.</p><p> </p>

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Response-Guided Neoadjuvant Chemotherapy for Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2012.45.0940 ◽

2013 ◽

Vol 31 (29) ◽

pp. 3623-3630 ◽

Cited By ~ 177

Author(s):

Gunter von Minckwitz ◽

Jens Uwe Blohmer ◽

Serban Dan Costa ◽

Carsten Denkert ◽

Holger Eidtmann ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Early Breast Cancer ◽

Hormone Receptor ◽

Triple Negative ◽

Pathologic Complete Response ◽

Exploratory Analysis ◽

Her2 Positive ◽

Luminal B ◽

Hormone Receptor Positive

Purpose We investigated disease-free survival (DFS) and overall survival (OS) after response-guided neoadjuvant chemotherapy in patients with early breast cancer. Patients and Methods We treated 2,072 patients with two cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC) and randomly assigned early responders to four (n = 704) or six (n = 686) additional TAC cycles, and early nonresponders to four cycles of TAC (n = 321) or vinorelbine and capecitabine (NX; n = 301) before surgery. Results DFS was longer in early responders receiving TAC × 8 than in those receiving TAC × 6 (hazard ratio [HR], 0.78; 95% CI, 0.62 to 0.97; P = .026), and in early nonresponders receiving TAC-NX than in those receiving TAC × 6 (HR, 0.59; 95% CI, 0.49 to 0.82; P = .001). Exploratory analysis showed that DFS after response-guided chemotherapy (TAC × 8 or TAC-NX) was significantly longer (HR, 0.71; 95% CI, 0.60 to 0.85; P < .003), as was OS (HR, 0.79; 95% CI, 0.63 to 0.99; P = .048), than on conventional chemotherapy (TAC × 6). DFS was longer after response-guided chemotherapy in all hormone receptor–positive tumors (luminal A HR = 0.55, luminal B [human epidermal growth factor receptor 2 (HER2) negative] HR = 0.40, and luminal B [HER2 positive] HR = 0.56), but not in hormone receptor–negative tumors (HER2 positive [nonluminal] HR = 1.01 and triple negative HR = 0.87). Pathologic complete response did not predict these survival effects. pCR predicted an improved DFS in triple-negative (HR = 6.67), HER2-positive (nonluminal; HR 5.24), or luminal B (HER2-negative) tumors (HR = 3.74). Conclusion This exploratory analysis suggests that response-guided neoadjuvant chemotherapy might improve survival and is most effective in hormone receptor–positive tumors. If confirmed, the response-guided approach could provide a clinically meaningful advantage for the neoadjuvant over the adjuvant approach in early breast cancer.

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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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