T Fujii1, T Kogawa1, W Dong2, A A Sahin3, S Moulder1, J K Litton1, D Tripathy1, T Iwamoto4, K K Hunt5, L Pusztai6, B Lim1, Y Shen2, N T Ueno7. 1. Department of Breast Medical Oncology. 2. Department of Biostatistics. 3. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA. 4. Department of Breast and Endocrine Surgery, Okayama University, Okayama, Japan. 5. Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston. 6. Department of Breast Medical Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, USA. 7. Department of Breast Medical Oncology. Electronic address: nueno@mdanderson.org.
Abstract
BACKGROUND: Although 1% has been used as cut-off for estrogen receptor (ER) positivity, several studies have reported that tumors with ER < 1% have characteristics similar to those with 1% ≤ ER < 10%. We hypothesized that in patients with human epidermal growth factor 2 (HER2)-negative breast cancer, a cut-off of 10% is more useful than one of 1% in discriminating for both a better pathological complete response (pCR) rate to neoadjuvant chemotherapy and a better long-term outcome with adjuvant hormonal therapy. Our objectives were to identify a percentage of ER expression below which pCR was likely and to determine whether this cut-off value can identify patients who would benefit from adjuvant hormonal therapy. PATIENTS AND METHODS: Patients with stage II or III HER2-negative primary breast cancer who received neoadjuvant chemotherapy followed by definitive surgery between June 1982 and June 2013 were included. Logistic regression models were used to assess the association between each variable and pCR. Cox models were used to analyze time to recurrence and overall survival. The recursive partitioning and regression trees method was used to calculate the cut-off value of ER expression. RESULTS: A total of 3055 patients were analyzed. Low percentage of ER was significantly associated with high pCR rate (OR = 0.99, 95% CI = 0.986-0.994, P < 0.001). The recommended cut-off of ER expression below which pCR was likely was 9.5%. Among patients with ER ≥ 10% tumors, but not those with 1%≤ER < 10% tumors, adjuvant hormonal therapy was significantly associated with long time to recurrence (HR = 0.24, 95% CI = 0.16-0.36, P < 0.001) and overall survival (HR = 0.32, 95% CI = 0.2-0.5, P < 0.001). CONCLUSION: Stage II or III HER2-negative primary breast cancer with ER < 10% behaves clinically like triple-negative breast cancer in terms of pCR and survival outcomes and patients with such tumors may have a limited benefit from adjuvant hormonal therapy. It may be more clinically relevant to define triple-negative breast cancer as HER2-negative breast cancer with <10%, rather than <1%, of ER and/or progesterone receptor expression.
BACKGROUND: Although 1% has been used as cut-off for estrogen receptor (ER) positivity, several studies have reported that tumors with ER < 1% have characteristics similar to those with 1% ≤ ER < 10%. We hypothesized that in patients with human epidermal growth factor 2 (HER2)-negative breast cancer, a cut-off of 10% is more useful than one of 1% in discriminating for both a better pathological complete response (pCR) rate to neoadjuvant chemotherapy and a better long-term outcome with adjuvant hormonal therapy. Our objectives were to identify a percentage of ER expression below which pCR was likely and to determine whether this cut-off value can identify patients who would benefit from adjuvant hormonal therapy. PATIENTS AND METHODS: Patients with stage II or III HER2-negative primary breast cancer who received neoadjuvant chemotherapy followed by definitive surgery between June 1982 and June 2013 were included. Logistic regression models were used to assess the association between each variable and pCR. Cox models were used to analyze time to recurrence and overall survival. The recursive partitioning and regression trees method was used to calculate the cut-off value of ER expression. RESULTS: A total of 3055 patients were analyzed. Low percentage of ER was significantly associated with high pCR rate (OR = 0.99, 95% CI = 0.986-0.994, P < 0.001). The recommended cut-off of ER expression below which pCR was likely was 9.5%. Among patients with ER ≥ 10% tumors, but not those with 1%≤ER < 10% tumors, adjuvant hormonal therapy was significantly associated with long time to recurrence (HR = 0.24, 95% CI = 0.16-0.36, P < 0.001) and overall survival (HR = 0.32, 95% CI = 0.2-0.5, P < 0.001). CONCLUSION: Stage II or III HER2-negative primary breast cancer with ER < 10% behaves clinically like triple-negative breast cancer in terms of pCR and survival outcomes and patients with such tumors may have a limited benefit from adjuvant hormonal therapy. It may be more clinically relevant to define triple-negative breast cancer as HER2-negative breast cancer with <10%, rather than <1%, of ER and/or progesterone receptor expression.
Authors: M Yi; L Huo; K B Koenig; E A Mittendorf; F Meric-Bernstam; H M Kuerer; I Bedrosian; A U Buzdar; W F Symmans; J R Crow; M Bender; R R Shah; G N Hortobagyi; K K Hunt Journal: Ann Oncol Date: 2014-02-20 Impact factor: 32.976
Authors: Olga Karginova; Marni B Siegel; Amanda E D Van Swearingen; Allison M Deal; Barbara Adamo; Maria J Sambade; Soha Bazyar; Nana Nikolaishvili-Feinberg; Ryan Bash; Sara O'Neal; Katie Sandison; Joel S Parker; Charlene Santos; David Darr; William Zamboni; Yueh Z Lee; C Ryan Miller; Carey K Anders Journal: Mol Cancer Ther Date: 2015-04 Impact factor: 6.261
Authors: M De Laurentiis; D Cianniello; R Caputo; B Stanzione; G Arpino; S Cinieri; V Lorusso; S De Placido Journal: Cancer Treat Rev Date: 2010-11 Impact factor: 12.111
Authors: Lyndsay N Harris; Nofisat Ismaila; Lisa M McShane; Fabrice Andre; Deborah E Collyar; Ana M Gonzalez-Angulo; Elizabeth H Hammond; Nicole M Kuderer; Minetta C Liu; Robert G Mennel; Catherine Van Poznak; Robert C Bast; Daniel F Hayes Journal: J Clin Oncol Date: 2016-02-08 Impact factor: 44.544
Authors: Mitch Dowsett; Torsten O Nielsen; Roger A'Hern; John Bartlett; R Charles Coombes; Jack Cuzick; Matthew Ellis; N Lynn Henry; Judith C Hugh; Tracy Lively; Lisa McShane; Soon Paik; Frederique Penault-Llorca; Ljudmila Prudkin; Meredith Regan; Janine Salter; Christos Sotiriou; Ian E Smith; Giuseppe Viale; Jo Anne Zujewski; Daniel F Hayes Journal: J Natl Cancer Inst Date: 2011-09-29 Impact factor: 13.506
Authors: Halei C Benefield; Emma H Allott; Katherine E Reeder-Hayes; Charles M Perou; Lisa A Carey; Joseph Geradts; Xuezheng Sun; Benjamin C Calhoun; Melissa A Troester Journal: J Natl Cancer Inst Date: 2020-07-01 Impact factor: 13.506
Authors: Tal Sella; Shari I Gelber; Philip D Poorvu; Hee-Jeong Kim; Laura Dominici; Yaileen D Guzman-Arocho; Laura Collins; Kathryn J Ruddy; Rulla M Tamimi; Jeffrey M Peppercorn; Lidia Schapira; Virginia F Borges; Steven E Come; Ellen Warner; Craig Snow; Debbie M Jakubowski; Christy A Russell; Eric P Winer; Shoshana M Rosenberg; Ann H Partridge Journal: Breast Cancer Res Treat Date: 2020-11-04 Impact factor: 4.872
Authors: Grace G Bushnell; Abhijeet P Deshmukh; Petra den Hollander; Ming Luo; Rama Soundararajan; Dongya Jia; Herbert Levine; Sendurai A Mani; Max S Wicha Journal: NPJ Breast Cancer Date: 2021-05-28
Authors: Fangyuan Zhao; Brenda Copley; Qun Niu; Fang Liu; Julie A Johnson; Thomas Sutton; Galina Khramtsova; Elisabeth Sveen; Toshio F Yoshimatsu; Yonglan Zheng; Abiola Ibraheem; Nora Jaskowiak; Rita Nanda; Gini F Fleming; Olufunmilayo I Olopade; Dezheng Huo Journal: Breast Cancer Res Treat Date: 2020-10-27 Impact factor: 4.872
Authors: Tamera J Lillemoe; Mara Rendi; Michaela L Tsai; Monica Knaack; Rina Yarosh; Erin Grimm; Barbara Susnik; Janet Krueger; Susan Olet; Karen K Swenson Journal: Int J Breast Cancer Date: 2021-05-24
Authors: Hesham Elghazaly; Hope S Rugo; Hamdy A Azim; Sandra M Swain; Banu Arun; Matti Aapro; Edith A Perez; Benjamin O Anderson; Frederique Penault-Llorca; Pierfranco Conte; Nagi S El Saghir; Cheng-Har Yip; Marwan Ghosn; Philip Poortmans; Mohamed A Shehata; Armando E Giuliano; Jessica W T Leung; Valentina Guarneri; Joseph Gligorov; Bahadir M Gulluoglu; Hany Abdel Aziz; Mona Frolova; Mohamed Sabry; Charles M Balch; Roberto Orecchia; Heba M El-Zawahry; Sana Al-Sukhun; Khaled Abdel Karim; Alaa Kandil; Ruslan M Paltuev; Meteb Foheidi; Mohamed El-Shinawi; Manal ElMahdy; Omalkhair Abulkhair; Wentao Yang; Adel T Aref; Joaira Bakkach; Nermean Bahie Eldin; Hagar Elghazawy Journal: Cancers (Basel) Date: 2021-05-08 Impact factor: 6.639