Definition and Impact of Pathologic Complete Response on Prognosis After Neoadjuvant Chemotherapy in Various Intrinsic Breast Cancer Subtypes

Minckwitz, Gϋnter von; Untch, Michael; Blohmer, Jens-Uwe; Costa, Serban Dan; Eidtmann, Holger; Fasching, Peter A.; Gerber, Bernd; Eiermann, W.; Hilfrich, J.; Huober, Jens; Jackisch, Christian; Kaufmann, M.; Konecny, Gottfried E.; Denkert, Carsten; Nekljudova, Valentina; Mehta, Keyur; Loibl, Sibylle

doi:10.1200/jco.2011.38.8595

Cited by 2,263 publications

(1,986 citation statements)

References 32 publications

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“…Within the ILC group, none of the survival endpoints were different between pCR and non-pCR patients after neoadjuvant chemotherapy. pCR is a surrogate endpoint for predicting long-term clinical benefit on endpoints such as disease-free or overall survival [9,30]. However, pCR seems especially important for tumours with more aggressive biological features.…”

Section: Discussionmentioning

confidence: 99%

“…Between 1998 and 2010, 9,197 breast cancer patients were enrolled in nine prospectively randomized multicentre, neoadjuvant trials in Germany, all having comparable main eligibility criteria [9,11,12].…”

Section: Methodsmentioning

confidence: 99%

“…In the GeparQuinto trial, patients in the HER2-negative setting were randomized to chemotherapy with or without bevacizumab [16]. In the Gepardo (no follow-up data) and Geparduo trial all patients received pre-surgical tamoxifen [9,17]. Adjuvant endocrine treatment was administered to all HR-positive patients and postsurgical radiotherapy was given according to effective guidelines [18].…”

Section: Methodsmentioning

confidence: 99%

“…The pathological complete response (pCR) rate after neoadjuvant chemotherapy (NACT) seems to be significantly lower in patients with ILC [8,9]. The overall clinical behaviour, however, seems to be better for ILC than for other histological types [10].…”

Section: Introductionmentioning

confidence: 99%

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Response and prognosis after neoadjuvant chemotherapy in 1,051 patients with infiltrating lobular breast carcinoma

Loibl

Volz

Mau

et al. 2014

Breast Cancer Res Treat

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Response and prognosis after neoadjuvant chemotherapy in 1,051 patients with infiltrating lobular breast carcinoma 123Breast Cancer Res Treat (2014) 144:153-162 DOI 10.1007/s10549-014-2861 pCR and this is not well correlated with further outcome. The mastectomy rate was considerably high in ILC patients even after obtaining a pCR. We, therefore, suggest to offer NACT mainly to ILC patients with HR-negative tumours.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Response and prognosis after neoadjuvant chemotherapy in 1,051 patients with infiltrating lobular breast carcinoma

Loibl

Volz

Mau

et al. 2014

Breast Cancer Res Treat

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“…Breast cancer subtypes were defined to histopathological characteristics such as receptor status and grading according to the St. Gallen classification and by von Minckwitz and colleagues (Goldhirsch et al ., 2013; von Minckwitz et al ., 2012). …”

Section: Methodsmentioning

confidence: 99%

TGFβ1 regulates HGF‐induced cell migration and hepatocyte growth factor receptor MET expression via C‐ets‐1 and miR‐128‐3p in basal‐like breast cancer

et al. 2018

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Breast cancer is the most common cancer in women worldwide. The tumor microenvironment contributes to tumor progression by inducing cell dissemination from the primary tumor and metastasis. TGFβ signaling is involved in breast cancer progression and is specifically elevated during metastatic transformation in aggressive breast cancer. In this study, we performed genomewide correlation analysis of TGFBR2 expression in a panel of 51 breast cancer cell lines and identified that MET is coregulated with TGFBR2. This correlation was confirmed at the protein level in breast cancer cell lines and human tumor tissues. Flow cytometric analysis of luminal and basal‐like breast cancer cell lines and examination of 801 tumor specimens from a prospective cohort of breast cancer patients using reverse phase protein arrays revealed that expression of TGFBR2 and MET is increased in basal‐like breast cancer cell lines, as well as in triple‐negative breast cancer tumor tissues, compared to other subtypes. Using real‐time cell analysis technology, we demonstrated that TGFβ1 triggered hepatocyte growth factor (HGF)‐induced and MET‐dependent migration in vitro. Bioinformatic analysis predicted that TGFβ1 induces expression of C‐ets‐1 as a candidate transcription factor regulating MET expression. Indeed, TGFβ1‐induced expression of ETS1 and breast cancer cell migration was blocked by knockdown of ETS1. Further, we identified that MET is a direct target of miR‐128‐3p and that this miRNA is negatively regulated by TGFβ1. Overexpression of miR‐128‐3p reduced MET expression and abrogated HGF‐induced cell migration of invasive breast cancer cells. In conclusion, we have identified that TGFβ1 regulates HGF‐induced and MET‐mediated cell migration, through positive regulation of C‐ets‐1 and negative regulation of miR‐128‐3p expression in basal‐like breast cancer cell lines and in triple‐negative breast cancer tissue.

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Ten-Year Outcomes of Patients With Breast Cancer With Cytologically Confirmed Axillary Lymph Node Metastases and Pathologic Complete Response After Primary Systemic Chemotherapy

et al. 2016

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Importance The long-term impact of axillary pathologic complete response (pCR) on survival among women treated with primary systemic chemotherapy (PST) is unknown. Objective To assess the long-term impact of axillary pCR on relapse-free and overall survival. Design We retrospectively analyzed the impact of axillary pCR on 10-year overall (OS) and relapse-free survival (RFS) among women treated with PST at one institution. Women were stratified by post-PST axillary status, and survival outcomes were estimated and compared according to response in the breast and axilla. Setting A retrospective analysis of women who received neoadjuvant chemotherapy in a large U.S. comprehensive cancer center. Participants All women (N=1600) diagnosed with breast cancer stages II to III with cytologically confirmed axillary metastases between 1989 and 2007 who received PST at our institution were included. Main Outcome Measure Outcomes of interest were relapse-free and overall survival. Results Of 1600 women treated, 454 (28.4%) achieved axillary pCR. These patients were more likely to have HER2-positive and triple-negative disease, high-grade tumors, and lower clinical and pathologic T stage. Ten-year OS rates were 84% and 57% (P<.001) and 10-year RFS rates 79% and 50% (P<.001) for patients with axillary pCR and residual axillary disease, respectively. For patients with axillary pCR, 10-year OS rates were 90% for those with breast pCR and 72% for those with residual breast disease (P<.001). For patients with residual axillary disease, 10-year OS rates were 66% for patients with and 56% for patients without breast pCR (P=.02). Of patients receiving HER2-targeted therapy for HER2-positive disease, 67.1% (100/149) achieved axillary pCR; 10-year OS rates were 92% and 57% (P=.006) and 10-year RFS rates 89% and 44% (P<.001) for those with axillary pCR and residual axillary disease, respectively. Conclusion and Relevance Axillary pCR is associated with improved 10-year OS and RFS. Patients with axillary and breast pCR after PST have superior long-term survival outcomes. Patients undergoing HER2-targeted therapy for HER2-positive disease had high rates of axillary pCR, and those with axillary pCR had excellent 10-year overall survival.

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Definition and Impact of Pathologic Complete Response on Prognosis After Neoadjuvant Chemotherapy in Various Intrinsic Breast Cancer Subtypes

Cited by 2,263 publications

References 32 publications

Response and prognosis after neoadjuvant chemotherapy in 1,051 patients with infiltrating lobular breast carcinoma

Response and prognosis after neoadjuvant chemotherapy in 1,051 patients with infiltrating lobular breast carcinoma

TGFβ1 regulates HGF‐induced cell migration and hepatocyte growth factor receptor MET expression via C‐ets‐1 and miR‐128‐3p in basal‐like breast cancer

Ten-Year Outcomes of Patients With Breast Cancer With Cytologically Confirmed Axillary Lymph Node Metastases and Pathologic Complete Response After Primary Systemic Chemotherapy

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