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Prognostic significance of progesterone receptor levels in luminal-like Her2- early breast cancer patients. A retrospective single cancer center analysis
abstracts 247P
Prognostic significance of progesterone receptor levels in luminal-like Her2- early breast cancer patients. A retrospective single cancer center analysis
A. Diana, F. Carlino, E. Franzese, S. Centonze, L.P. Guerrera, A. Perrone, F. De Vita, F. Ciardiello, M. Orditura Department of Precision Medicine, Universit a degli Studi della Campania Luigi Vanvitelli, Naples, Italy
Italfarmaco. F. Carlino: Travel / Accommodation / Expenses: Italfarmaco, Gentili. E. Franzese: Travel / Accommodation / Expenses: Roche. S. Centonze: Travel / Accommodation / Expenses: Thesaro, Roche, Gentili. F. De Vita: Advisory / Consultancy: Roche, Amgen, Celgene, Lilly. F. Ciardiello: Advisory / Consultancy: Merck, Roche, Lilly, Bayer, Amgen, Pfizer, Servier. M. Orditura: Honoraria (self): Epionpharma, Italfarmaco; Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): EISAI. All other authors have declared no conflicts of interest.
248P
PAM50 HER2-enriched subtype and pathological complete response in HER2-positive early breast cancer: A meta-analysis
F. Schettini1, T. Pascual1, N. Chic1, B. Conte2, O. Martınez1, B. Adamo1, M. Vidal1, M. Mu~ noz1, A. Fernandez-Martınez3, G. Griguolo4, V. Guarneri4, P.F. Conte4, S. De Placido5, L. Carey6, C.M. Perou7, A. Prat1 1 Medical Oncology, Hospital Clinic, Barcelona, Spain, 2Medical Oncology, Ospedale Policlinico San Martino, University of Genova, Genoa, Italy, 3Medicine, University of North Carolina, Chapel Hill, NC, USA, 4Surgery, Oncology and Gastroenterology, Istituto Oncologico Veneto IRCCS, Padua, Italy, 5Clinical Medicine and Surgery, Azienda Universitaria Ospedaliera Federico II, Naples, Italy, 6Medicine - Division of Hematology/ Oncology, UNC - Lineberger Cancer Center, Chapel Hill, NC, USA, 7Genetics, UNC Lineberger Cancer Center, Chapel Hill, NC, USA Background: HER2-positive (HER2þ) breast cancer (BC) comprises all the intrinsic molecular subtypes, with the HER2-enriched (HER2-E) usually being the most represented. Data coming from neoadjuvant trials of HER2þ BC treated with anti-HER2 containing regimens, with or without chemotherapy (CT), have shown that HER2-E tumors are more likely to achieve pathologic complete response (pCR) than nonHER2-E tumors. We decided to perform a meta-analysis combining all the available data in attempt to validate the ability of the HER2-E signature to predict pCR. Methods: A systematic literature search was performed to identify clinical studies exploring the correlation between BC subtypes and pCR after neoadjuvant therapy (NAT) with anti-HER2 containing regimens in patients affected by HER2þ early BC. Primary analysis compared the association of gene signatures with pCR. Secondary
v82 | Breast Cancer, Early Stage
analyses compared the association of gene signatures with pCR within hormone receptor (HR) positive (þ) or negative (-) BC. Odds Ratio (OR) and 95% confidence intervals (CI) for pCR were extracted from each trial. A random-effect model was applied. The Higgins’ I2 was used to quantify heterogeneity. Results: Sixteen studies (2,857 patients) were included; 4 investigated CT-free regimens. Various methods for assessing BC intrinsic subtypes were used across all trials. HER2-E subtype was significantly associated with pCR in all patients (OR: 3.32, 95% CI: 2.70-4.07, p < 0.001, I2¼25%) and in HR þ (OR: 3.40, 2.51-4.61, p < 0.001, I2¼0%) and HR- (OR: 1.97, 1.10-3.54, p ¼ 0.02, I2¼46%) disease. In CT-free studies, HER2-E subtype was significantly associated with pCR in all patients (OR: 4.43, 2.348.38, p < 0.001, I2¼0%) and in HRþ disease (OR: 4.79, 2.23-10.29, p < 0.001, I2¼0%), but not within HR- tumors (OR: 2.18, 0.66-7.26, p ¼ 0.20). Conclusions: HER2-E subtype identifies patients with a higher likelihood of achieving a pCR following anti-HER2-based NAT, with or without CT. In the latter case, albeit limited by small casuistry, the association seems stronger in HRþ tumors. This suggests that strategies to escalate or de-escalate systemic therapy in HER2þ tumors would benefit from incorporating intrinsic subtypes. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: F. Schettini: Travel / Accommodation / Expenses: Pfizer and Celgene. T. Pascual: Advisory / Consultancy: Roche. P.F. Conte: Honoraria (self): BMS, Roche, EliLilly, Novartis, AstraZeneca; Advisory / Consultancy: Novartis, EliLilly, AstraZeneca, Tesaro; Research grant / Funding (self): Novartis, Roche, BMS, Merck-KGa; Research grant / Funding (self): Italian Ministry of Health, Veneto Secretary of Health, University of Padua. S. De Placido: Honoraria (self): Roche, Pfizer, AstraZeneca, Novartis, Celgene, Lilly and Eisai. L. Carey: Research grant / Funding (institution): Genentech / Roche, Novartis, Seattle Genetics, G1 Therapeutics, Immunomedics, Innocrin. C.M. Perou: Shareholder / Stockholder / Stock options: BioClassifier LLC; Advisory / Consultancy: BioClassifier LLC; Licensing / Royalties: Breast PAM50. A. Prat: Full / Part-time employment, An immediate family member employed: Novartis; Honoraria (self): Pfizer, Novartis, Roche, MSD Oncology, Lilly and Daiichi Sankyo; Advisory / Consultancy: NanoString Technologies, Amgen, Roche, Novartis, Pfizer and Bristol-Myers Squibb; Research grant / Funding (self): Roche, Novartis; Travel / Accommodation / Expenses: Daiichi Sankyo. All other authors have declared no conflicts of interest.
249P
Assessment of CPS1EG, neo-bioscore and modified neo-bioscore in breast cancer patients treated with preoperative systemic therapy: A multicenter cohort study
L. XU1, Y. Liu1, Z. Fan2, Z. Jiang3, Y. Liu4, R. Ling5, J. Zhang6, Z. Yu7, F. Jin8, C. Wang9, S. Cui10, S. Wang11, D. Mao12, Q. Xiang13, Z. Zhang13, B. Zhou1, Z. Liu14, C. Ma14, X. Duan1, Y. Cui13 1 Breast Disease Center, Peking University First Hospital, Beijing, China, 2Department of Breast Surgery, The First Hospital of Jilin University, Changchun, China, 3Department of Breast Cancer, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China, 4Hebei Breast Cancer Center, The 4th Hospital of Hebei Medical University, Shijiazhuang, China, 5Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Air Force (Military) Medical University, Xi’an, China, 6Breast Disease Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, China, 7 Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, China, 8Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, China, 9Department of Breast Surgery, Affiliated Union Hospital of Fujian Medical University, Fuzhou, China, 10Department of Breast Surgery, Affiliated Tumour Hospital of Zhengzhou University, Zhengzhou, China, 11Breast Center, Peking University People’s Hospital, Beijing, China, 12Department of Breast Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, China, 13Department Of Pharmacy, Peking University First Hospital, Beijing, China, 14Institute of Mental Health, Peking University, Beijing, China Background: An accurate prognostic assessment of breast cancer patients after preoperative systemic therapy (PST) is critical for physicians to adjust the systemic treatments. While both CPSþEG and Neo-Bioscore provide a satisfactory prediction, they, however, have limitations due to the lack of targeted therapies in current clinical practice. Methods: A retrospective multicenter cohort study was conducted from 12 participating hosipitals’ databases from 2006 to 2015. Five-year disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) were calculated using the KaplanMeier Method. Area under the curve (AUC) of the three staging systems was compared. The detailed staging systems are summarized in Table. Wald test and maximum likelihood estimates in Cox proportional hazards model was used for multivariate analysis.
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz240.071/5576295 by guest on 24 October 2019
Background: The prognostic role of Progesterone receptor (PR) expression in early invasive breast cancer (BC) remains controversial. The aim of this retrospective analysis was to investigate the impact of PR expression levels on outcome of patients with luminal-like Her2 negative early BC. Methods: A population cohort of 441 primary invasive ERþ/Her2- early BC patients from a single cancer center underwent surgery and received adjuvant endocrine therapy from 2000 to 2017 was retrieved. To assess the impact of the different PR levels on the prognosis, we calculated the Distant Free Survival (DFS) and the Breast Cancer Specific Survival (BCSS) according to 4 subtypes established on the basis of Ki67 value and PR expression rate (Subtype 1: PR 20%/Ki67<20%; Subtype 2: PR 20%/Ki6720%; Subtype 3: PR < 20%/Ki6720%; Subtype 4: PR < 20%/Ki67<20%). Cox regression analysis was used to correlate tumor characteristics with DFS and BCSS. Results: The rates of progression disease were 8%, 19%, 30% and 12% in subtype 1, 2, 3 and 4, respectively. Low PR expression (<20%) resulted an independent poor prognostic factor for DFS in patients with high Ki67 value (20%). The median DFS was 12.6 months and 10.1 months in subtype 2 and subtype 3, respectively (p ¼ 0.025) (Fig.1). The rates of cancer death were 5%, 12%, 24% and 12 % in subtype 1, 2, 3 and 4, respectively. Consistent with DFS results, a statistically significant correlation of PR expression level and BCSS was reported in patients with high Ki67 index (the median BCSS was 12.9 months in subtype 2 versus 10.5 months in subtype 3, respectively) (p ¼ 0.04). No correlations between survival and PR expression were demonstrated in patients with low Ki67 value (<20%), probably due to the small sample size in the subtypes 1 and 4 groups. Conclusions: Our study revealed different outcomes among patients with early BC according to different PR expression levels. Noteworthy, in patients with Ki67 20%, low PR expression levels (<20%) could be considered as a prognostic marker suggesting to re-evaluate PR status as a potential therapeutic guide in ERþ/Her2- early BC. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: A. Diana: Travel / Accommodation / Expenses: Ipsen, Novartis, Pharmamar,
Annals of Oncology
Prognostic significance of progesterone receptor levels in luminal-like Her2- early breast cancer patients. A retrospective single cancer center analysis
A. Diana, F. Carlino, E. Franzese, S. Centonze, L.P. Guerrera, A. Perrone, F. De Vita, F. Ciardiello, M. Orditura Department of Precision Medicine, Universit a degli Studi della Campania Luigi Vanvitelli, Naples, Italy
Italfarmaco. F. Carlino: Travel / Accommodation / Expenses: Italfarmaco, Gentili. E. Franzese: Travel / Accommodation / Expenses: Roche. S. Centonze: Travel / Accommodation / Expenses: Thesaro, Roche, Gentili. F. De Vita: Advisory / Consultancy: Roche, Amgen, Celgene, Lilly. F. Ciardiello: Advisory / Consultancy: Merck, Roche, Lilly, Bayer, Amgen, Pfizer, Servier. M. Orditura: Honoraria (self): Epionpharma, Italfarmaco; Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): EISAI. All other authors have declared no conflicts of interest.
248P
PAM50 HER2-enriched subtype and pathological complete response in HER2-positive early breast cancer: A meta-analysis
F. Schettini1, T. Pascual1, N. Chic1, B. Conte2, O. Martınez1, B. Adamo1, M. Vidal1, M. Mu~ noz1, A. Fernandez-Martınez3, G. Griguolo4, V. Guarneri4, P.F. Conte4, S. De Placido5, L. Carey6, C.M. Perou7, A. Prat1 1 Medical Oncology, Hospital Clinic, Barcelona, Spain, 2Medical Oncology, Ospedale Policlinico San Martino, University of Genova, Genoa, Italy, 3Medicine, University of North Carolina, Chapel Hill, NC, USA, 4Surgery, Oncology and Gastroenterology, Istituto Oncologico Veneto IRCCS, Padua, Italy, 5Clinical Medicine and Surgery, Azienda Universitaria Ospedaliera Federico II, Naples, Italy, 6Medicine - Division of Hematology/ Oncology, UNC - Lineberger Cancer Center, Chapel Hill, NC, USA, 7Genetics, UNC Lineberger Cancer Center, Chapel Hill, NC, USA Background: HER2-positive (HER2þ) breast cancer (BC) comprises all the intrinsic molecular subtypes, with the HER2-enriched (HER2-E) usually being the most represented. Data coming from neoadjuvant trials of HER2þ BC treated with anti-HER2 containing regimens, with or without chemotherapy (CT), have shown that HER2-E tumors are more likely to achieve pathologic complete response (pCR) than nonHER2-E tumors. We decided to perform a meta-analysis combining all the available data in attempt to validate the ability of the HER2-E signature to predict pCR. Methods: A systematic literature search was performed to identify clinical studies exploring the correlation between BC subtypes and pCR after neoadjuvant therapy (NAT) with anti-HER2 containing regimens in patients affected by HER2þ early BC. Primary analysis compared the association of gene signatures with pCR. Secondary
v82 | Breast Cancer, Early Stage
analyses compared the association of gene signatures with pCR within hormone receptor (HR) positive (þ) or negative (-) BC. Odds Ratio (OR) and 95% confidence intervals (CI) for pCR were extracted from each trial. A random-effect model was applied. The Higgins’ I2 was used to quantify heterogeneity. Results: Sixteen studies (2,857 patients) were included; 4 investigated CT-free regimens. Various methods for assessing BC intrinsic subtypes were used across all trials. HER2-E subtype was significantly associated with pCR in all patients (OR: 3.32, 95% CI: 2.70-4.07, p < 0.001, I2¼25%) and in HR þ (OR: 3.40, 2.51-4.61, p < 0.001, I2¼0%) and HR- (OR: 1.97, 1.10-3.54, p ¼ 0.02, I2¼46%) disease. In CT-free studies, HER2-E subtype was significantly associated with pCR in all patients (OR: 4.43, 2.348.38, p < 0.001, I2¼0%) and in HRþ disease (OR: 4.79, 2.23-10.29, p < 0.001, I2¼0%), but not within HR- tumors (OR: 2.18, 0.66-7.26, p ¼ 0.20). Conclusions: HER2-E subtype identifies patients with a higher likelihood of achieving a pCR following anti-HER2-based NAT, with or without CT. In the latter case, albeit limited by small casuistry, the association seems stronger in HRþ tumors. This suggests that strategies to escalate or de-escalate systemic therapy in HER2þ tumors would benefit from incorporating intrinsic subtypes. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: F. Schettini: Travel / Accommodation / Expenses: Pfizer and Celgene. T. Pascual: Advisory / Consultancy: Roche. P.F. Conte: Honoraria (self): BMS, Roche, EliLilly, Novartis, AstraZeneca; Advisory / Consultancy: Novartis, EliLilly, AstraZeneca, Tesaro; Research grant / Funding (self): Novartis, Roche, BMS, Merck-KGa; Research grant / Funding (self): Italian Ministry of Health, Veneto Secretary of Health, University of Padua. S. De Placido: Honoraria (self): Roche, Pfizer, AstraZeneca, Novartis, Celgene, Lilly and Eisai. L. Carey: Research grant / Funding (institution): Genentech / Roche, Novartis, Seattle Genetics, G1 Therapeutics, Immunomedics, Innocrin. C.M. Perou: Shareholder / Stockholder / Stock options: BioClassifier LLC; Advisory / Consultancy: BioClassifier LLC; Licensing / Royalties: Breast PAM50. A. Prat: Full / Part-time employment, An immediate family member employed: Novartis; Honoraria (self): Pfizer, Novartis, Roche, MSD Oncology, Lilly and Daiichi Sankyo; Advisory / Consultancy: NanoString Technologies, Amgen, Roche, Novartis, Pfizer and Bristol-Myers Squibb; Research grant / Funding (self): Roche, Novartis; Travel / Accommodation / Expenses: Daiichi Sankyo. All other authors have declared no conflicts of interest.
249P
Assessment of CPS1EG, neo-bioscore and modified neo-bioscore in breast cancer patients treated with preoperative systemic therapy: A multicenter cohort study
L. XU1, Y. Liu1, Z. Fan2, Z. Jiang3, Y. Liu4, R. Ling5, J. Zhang6, Z. Yu7, F. Jin8, C. Wang9, S. Cui10, S. Wang11, D. Mao12, Q. Xiang13, Z. Zhang13, B. Zhou1, Z. Liu14, C. Ma14, X. Duan1, Y. Cui13 1 Breast Disease Center, Peking University First Hospital, Beijing, China, 2Department of Breast Surgery, The First Hospital of Jilin University, Changchun, China, 3Department of Breast Cancer, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China, 4Hebei Breast Cancer Center, The 4th Hospital of Hebei Medical University, Shijiazhuang, China, 5Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Air Force (Military) Medical University, Xi’an, China, 6Breast Disease Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, China, 7 Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, China, 8Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, China, 9Department of Breast Surgery, Affiliated Union Hospital of Fujian Medical University, Fuzhou, China, 10Department of Breast Surgery, Affiliated Tumour Hospital of Zhengzhou University, Zhengzhou, China, 11Breast Center, Peking University People’s Hospital, Beijing, China, 12Department of Breast Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, China, 13Department Of Pharmacy, Peking University First Hospital, Beijing, China, 14Institute of Mental Health, Peking University, Beijing, China Background: An accurate prognostic assessment of breast cancer patients after preoperative systemic therapy (PST) is critical for physicians to adjust the systemic treatments. While both CPSþEG and Neo-Bioscore provide a satisfactory prediction, they, however, have limitations due to the lack of targeted therapies in current clinical practice. Methods: A retrospective multicenter cohort study was conducted from 12 participating hosipitals’ databases from 2006 to 2015. Five-year disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) were calculated using the KaplanMeier Method. Area under the curve (AUC) of the three staging systems was compared. The detailed staging systems are summarized in Table. Wald test and maximum likelihood estimates in Cox proportional hazards model was used for multivariate analysis.
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz240.071/5576295 by guest on 24 October 2019
Background: The prognostic role of Progesterone receptor (PR) expression in early invasive breast cancer (BC) remains controversial. The aim of this retrospective analysis was to investigate the impact of PR expression levels on outcome of patients with luminal-like Her2 negative early BC. Methods: A population cohort of 441 primary invasive ERþ/Her2- early BC patients from a single cancer center underwent surgery and received adjuvant endocrine therapy from 2000 to 2017 was retrieved. To assess the impact of the different PR levels on the prognosis, we calculated the Distant Free Survival (DFS) and the Breast Cancer Specific Survival (BCSS) according to 4 subtypes established on the basis of Ki67 value and PR expression rate (Subtype 1: PR 20%/Ki67<20%; Subtype 2: PR 20%/Ki6720%; Subtype 3: PR < 20%/Ki6720%; Subtype 4: PR < 20%/Ki67<20%). Cox regression analysis was used to correlate tumor characteristics with DFS and BCSS. Results: The rates of progression disease were 8%, 19%, 30% and 12% in subtype 1, 2, 3 and 4, respectively. Low PR expression (<20%) resulted an independent poor prognostic factor for DFS in patients with high Ki67 value (20%). The median DFS was 12.6 months and 10.1 months in subtype 2 and subtype 3, respectively (p ¼ 0.025) (Fig.1). The rates of cancer death were 5%, 12%, 24% and 12 % in subtype 1, 2, 3 and 4, respectively. Consistent with DFS results, a statistically significant correlation of PR expression level and BCSS was reported in patients with high Ki67 index (the median BCSS was 12.9 months in subtype 2 versus 10.5 months in subtype 3, respectively) (p ¼ 0.04). No correlations between survival and PR expression were demonstrated in patients with low Ki67 value (<20%), probably due to the small sample size in the subtypes 1 and 4 groups. Conclusions: Our study revealed different outcomes among patients with early BC according to different PR expression levels. Noteworthy, in patients with Ki67 20%, low PR expression levels (<20%) could be considered as a prognostic marker suggesting to re-evaluate PR status as a potential therapeutic guide in ERþ/Her2- early BC. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: A. Diana: Travel / Accommodation / Expenses: Ipsen, Novartis, Pharmamar,
Annals of Oncology