BACKGROUND Estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor -2 (HER2) statuses are clinically used to select treatments. Several studies reported that discordance between primary and metastatic lesions lead to detrimental outcome. Although biopsy of recurrent breast cancer has been recently recommended by international clinical guidelines, prognostic relevance remains to be elucidated. The aim of the present study is to evaluate response to treatment and prognosis of patients with receptor discordance, compared with patients with receptor concordance. Patients and METHODS We retrospectively identified recurrent breast cancer patients who had biopsies or resections of recurrent lesions between January 2007 and April 2012 at Keio University Hospital. HR status was assessed by immunohistochemistry (IHC) and determined using the Allred score. HR status was defined as positive when score was 3 and more. HER2 status was assessed by IHC and fluorescence in situ hybridization (FISH) analysis. We defined HER2 positivity as 3+ staining intensity by IHC or the presence of HER2 gene amplification by FISH. Tumors were classified as luminal (HR+ and HER2-), luminal/HER2 (HR+ and HER2+), HER2 (HR- and HER2+), or triple negative (HR- and HER2-). Treatment was decided according to the receptor status of recurrent tumors. RESULTS Among 38 patients undergoing biopsy or resection, 13.2% (5) were loco-regional recurrences and 86.8% (33) were distant metastases (lung 21; liver 6; brain 3; pleura 1). Overall, 10 patients (26.3%) changed subtypes at recurrent lesions (table1) and all of them had a change in treatment plan. Discordance in subtype between primary tumor and recurrent lesion Recurrent lesion (%) LuminalLuminal/HER2HER2Triple negativeDiscordance rate (%)Primary tumor (%)Luminal18 (66.7)2 (8.3)1(4.2)3(12.5)6/24 (25.0)Luminal/HER21 (14.3)6 (85.7)001/7 (14.3)HER201 (100.0)001/1 (100.0)Triple negative1 (16.7)1 (16.7)04(66.7)2/6 (33.3)Total20101710/38 (26.3) Changes in management included the addition of trastuzumab in patients with gain of HER2 (n=3), the use of chemotherapy in those with loss of HR (n=6) and provision of endocrine therapy for those with gaining HR (n=3). Response rate of discordant group and concordant group were 10.0% and 21.4%, respectively (p=1.000). Clinical benefit rate of discordant group and concordant group were 40.0% and 67.9%, respectively (p=0.150). There is no significant difference of time to progression (TTP) between the discordant and concordant groups (169.5days vs.319.5days, p= 0.081). CONCLUSION Patients with receptor discordance tended towards worse response rate and shorter TTP, leading to the poor prognosis of the recurrent breast cancer patients with receptor discordance. Citation Format: Hanako Ueno, Hiromitsu Jinno, Takamichi Yokoe, Toshiaki Kurihara, Masaru Takemae, Aiko Nagayama, Maiko Takahashi, Tetsu Hayashida, Kaori Kameyama, Yuko Kitagawa. Response to treatment and prognosis of recurrent breast cancer patients with receptor discordance [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-13-11.
Background: Hormone receptor (Estrogen receptor (ER), Progesterone receptor (PgR)) is an important biological marker for predicting prognosis and making effective treatment decisions. Discordance in these biomarkers between the primary tumor and recurrent lesions is reported frequently. However, it is not well known whether these biomarkers are affected by neoadjuvant chemotherapy and their impacts on outcomes still remain to be elucidated. The aim of the present study is to evaluate the changes in HR status after neoadjuvant chemotherapy in patients with operable breast cancer and their relationship with response to treatment and prognosis. Patients and Methods: Of 162 patients with stage II/III breast cancer patients receiving neoadjuvant chemotherapy from January 2005 to September 2012 at Keio University Hospital, 140 patients with non-pCR were analyzed. Patients were treated with sequential anthracycline and taxane. ER and PgR were assessed in both CNB performed prior to neoadjuvant chemotherapy and surgical samples. HR status was assessed by immunohistochemistry (IHC). ER/PgR status was determined using the Allred score and defined as positive when score was 3 and more. HR status was considered positive in cases of ER and/or PgR positivity. Pathological response criteria were classified as grade 0, 1, 2, or 3: grade 0 includes almost no change in cancer cells; grade 1 includes slight or marked changes in less than two thirds of area; grade 2 includes marked changes in more than two thirds of area; grade3 includes necrosis or disappearance of all tumor cells. Results: ER, PgR and HR positive rates before neoadjuvant chemotherapy were 72.9%, 67.1% and 76.4%, respectively. Changes in ER, PgR and HR status between CNB and surgical samples were 12.1% (4.3% gain; 7.8% loss), 17.1% (2.1% gain; 15.0% loss) and 9.3% (2.9% gain; 6.4% loss), respectively. In ER-discordant group, grade 2 rate of pathological response was significantly higher than ER- concordant group (61.1% vs. 30%, p=0.033), whereas there were no significant differences of pathological response between discordant and concordant group in PgR status. In the disease free survival (DFS), there were no significant difference between concordance and discordance group for ER, PgR and HR (p=0.216, 0.859, 0.233) after a median follow-up of 40.4 months. But patients with a loss in ER and/or HR status had a trend to a shorter DFS compared with the concordant ER and/or HR-positive group (p=0.169 and 0.154) Conclusions: After neoadjuvant chemotherapy, discordance of biomarkers was seen in 5-20%. The pathological response was significantly associated with the change in ER status. A loss in ER and/or HR status may affect a prognosis of breast cancer after neoadjuvant chemotherapy, but still need further investigation. Citation Format: Toshiaki Kurihara, Hanako Ueno, Masaru Takemae, Aiko Nagayama, Maiko Takahashi, Tetsu Hayashida, Hiromitsu Jinno, Yuko Kitagawa. Prognostic impact of discordance in hormone receptor status after the neoadjuvant chemotherapy in primary breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-49.
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