Prognosis and endocrine therapy selection for patients with low hormone receptor‑positive breast cancer following neoadjuvant chemotherapy: A retrospective study of 570 patients in China

Ding,Yuqin; Ding,Kaijing; Yu,Kun; Zou,Dehong; Yang,Hongjian; He,Xiangming; Mo,Wenju; Yu,Xingfei; Ding,Xiaowen

doi:10.3892/ol.2019.11033

Prognosis and endocrine therapy selection for patients with low hormone receptor‑positive breast cancer following neoadjuvant chemotherapy: A retrospective study of 570 patients in China

Authors:
- Yuqin Ding
- Kaijing Ding
- Kun Yu
- Dehong Zou
- Hongjian Yang
- Xiangming He
- Wenju Mo
- Xingfei Yu
- Xiaowen Ding
View Affiliations

Affiliations: Department of Breast Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China, Department of Child Psychology, Zhejiang University Affiliated Mental Health Center, Hangzhou, Zhejiang 310013, P.R. China, Department of Thyroid Breast Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China
Published online on: November 1, 2019 https://doi.org/10.3892/ol.2019.11033
Pages: 6690-6696
Copyright: © Ding et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The 2010 American Society of Clinical Oncology guidelines have reduced the immunohistochemistry cut‑off value for determining estrogen receptor b positivity from 10 to 1% of stained cells in breast cancer. In clinical practice, low‑hormone receptor positive (low HR+) tumors are classified in the luminal subtype, although they exhibit aggressive features and poor prognosis. Information regarding the prognosis of patients with breast cancer following treatment with optimal endocrine therapy and neoadjuvant chemotherapy (NAC) is currently lacking. In the present study, the differences in clinical characteristics and survival of patients with breast cancer were compared among those with low and high HR+ breast cancer who received NAC. Furthermore, the effects of different types of endocrine therapies on the prognosis of patients with breast cancer were compared. The study population comprised patients with primary breast cancer who were treated at the Zhejiang Cancer Hospital between January, 2007 and December, 2017. Patients were divided into three groups based on the results of immunohistochemistry: HR+ (positive staining >10%), HR‑ (positive staining <1%) and low HR+ (positive staining 1‑10%). The low HR+ group was further divided into three subgroups according to the different endocrine therapies administered: Tamoxifen, aromatase inhibitor or no treatment. Among the 570 patients included in the present study, 60 (10.53%) patients had low HR+ tumors. With a median follow‑up of 48.98 months, patients with low HR+ tumors had reduced survival rates compared with those with HR+ tumors. Furthermore, the pathologic complete response rate (pCR) of patients with low HR+ was comprised between pCR from patients with HR+ and pCR from patients with HR‑ following NAC treatment. In addition, no significant difference in the overall prognosis was observed among patients with low HR+ following treatment with different endocrine therapies. Subsequently, patients in the low HR+ group were more likely to benefit from NAC compared with patients in the HR+ group. Intensive endocrine therapy may therefore improve the prognosis of patients with breast cancer and low HR+; however, further investigation is required.

View Figures

View References

1	Early Breast Cancer Trialists' Collaborative Group (EBCTCG), : Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet. 365:1687–1717. 2005. View Article : Google Scholar : PubMed/NCBI
2	Waks AG and Winer EP: Breast cancer treatment: A review. JAMA. 321:288–300. 2019. View Article : Google Scholar : PubMed/NCBI
3	Goldhirsch A, Glick JH, Gelber RD, Coates AS, Thürlimann B and Senn HJ; Panel members, : Meeting highlights: International expert consensus on the primary therapy of early breast cancer 2005. Ann Oncol. 16:1569–1583. 2005. View Article : Google Scholar : PubMed/NCBI
4	Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, et al: American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 28:2784–2795. 2010. View Article : Google Scholar : PubMed/NCBI
5	Gloyeske NC, Dabbs DJ and Bhargava R: Low ER+ breast cancer: Is this a distinct group? Am J Clin Pathol. 141:697–701. 2014. View Article : Google Scholar : PubMed/NCBI
6	Raghav KP, Hernandez-Aya LF, Lei X, Chavez-Macgregor M, Meric-Bernstam F, Buchholz TA, Sahin A, Do KA, Hortobagyi GN and Gonzalez-Angulo AM: Impact of low estrogen/progesterone receptor expression on survival outcomes in breast cancers previously classified as triple negative breast cancers. Cancer. 118:1498–1506. 2012. View Article : Google Scholar : PubMed/NCBI
7	Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I, Kuroi K, Im SA, Park BW, Kim SB, et al: Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med. 376:2147–2159. 2017. View Article : Google Scholar : PubMed/NCBI
8	Reddy SM, Barcenas CH, Sinha AK, Hsu L, Moulder SL, Tripathy D, Hortobagyi GN and Valero V: Long-term survival outcomes of triple-receptor negative breast cancer survivors who are disease free at 5 years and relationship with low hormone receptor positivity. Br J Cancer. 118:17–23. 2018. View Article : Google Scholar : PubMed/NCBI
9	Prabhu JS, Korlimarla A, Desai K, Alexander A, Raghavan R, Anupama C, Dendukuri N, Manjunath S, Correa M, Raman N, et al: A majority of low (1–10%) ER positive breast cancers behave like hormone receptor negative tumors. J Cancer. 5:156–165. 2014. View Article : Google Scholar : PubMed/NCBI
10	Landmann A, Farrugia DJ, Zhu L, Diego EJ, Johnson RR, Soran A, Dabbs DJ, Clark BZ, Puhalla SL, Jankowitz RC, et al: Low estrogen receptor (ER)-positive breast cancer and neoadjuvant systemic chemotherapy: Is response similar to typical ER-positive or ER-negative disease? Am J Clin Pathol. 150:34–42. 2018. View Article : Google Scholar : PubMed/NCBI
11	Yi M, Huo L, Koenig KB, Mittendorf EA, Meric-Bernstam F, Kuerer HM, Bedrosian I, Buzdar AU, 0Symmans WF, Crow JR, et al: Which threshold for ER positivity? a retrospective study based on 9639 patients. Ann Oncol. 25:1004–1011. 2014. View Article : Google Scholar : PubMed/NCBI
12	Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, Gershenwald JE, Compton CC, Hess KR, Sullivan DC, et al: AJCC cancer staging manual. New York: 2017, View Article : Google Scholar
13	von Minckwitz G, Raab G, Caputo A, Schütte M, Hilfrich J, Blohmer JU, Gerber B, Costa SD, Merkle E, Eidtmann H, et al: Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: The GEPARDUO study of the german breast group. J Clin Oncol. 23:2676–2685. 2005. View Article : Google Scholar : PubMed/NCBI
14	Bines J, Earl H, Buzaid AC and Saad ED: Anthracyclines and taxanes in the neo/adjuvant treatment of breast cancer: Does the sequence matter? Ann Oncol. 25:1079–1085. 2014. View Article : Google Scholar : PubMed/NCBI
15	Gradishar WJ, Anderson BO, Balassanian R, Blair SL, Burstein HJ, Cyr A, Elias AD, Farrar WB, Forero A, Giordano SH, et al: NCCN guidelines insights: Breast cancer, Version 1.2017. J Natl Compr Canc Netw. 15:433–451. 2017. View Article : Google Scholar : PubMed/NCBI
16	Prat A, Cheang MC, Martin M, Parker JS, Carrasco E, Caballero R, Tyldesley S, Gelmon K, Bernard PS, Nielsen TO and Perou CM: Prognostic significance of progesterone receptor-positive tumor cells within immunohistochemically defined luminal A breast cancer. J Clin Oncol. 31:203–209. 2013. View Article : Google Scholar : PubMed/NCBI
17	Bae SY, Kim S, Lee JH, Lee HC, Lee SK, Kil WH, Kim SW, Lee JE and Nam SJ: Poor prognosis of single hormone receptor- positive breast cancer: Similar outcome as triple-negative breast cancer. BMC Cancer. 15:1382015. View Article : Google Scholar : PubMed/NCBI
18	Cancello G, Maisonneuve P, Rotmensz N, Viale G, Mastropasqua MG, Pruneri G, Montagna E, Iorfida M, Mazza M, Balduzzi A, et al: Progesterone receptor loss identifies Luminal B breast cancer subgroups at higher risk of relapse. Ann Oncol. 24:661–668. 2013. View Article : Google Scholar : PubMed/NCBI
19	Braun L, Mietzsch F, Seibold P, Schneeweiss A, Schirmacher P, Chang-Claude J, Peter Sinn H and Aulmann S: Intrinsic breast cancer subtypes defined by estrogen receptor signalling-prognostic relevance of progesterone receptor loss. Mod Pathol. 26:1161–1171. 2013. View Article : Google Scholar : PubMed/NCBI
20	Guarneri V, Broglio K, Kau SW, Cristofanilli M, Buzdar AU, Valero V, Buchholz T, Meric F, Middleton L, Hortobagyi GN and Gonzalez-Angulo AM: Prognostic value of pathologic complete response after primary chemotherapy in relation to hormone receptor status and other factors. J Clin Oncol. 24:1037–1044. 2006. View Article : Google Scholar : PubMed/NCBI
21	Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, Ollila DW, Sartor CI, Graham ML and Perou CM: The triple negative paradox: Primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 13:2329–2334. 2007. View Article : Google Scholar : PubMed/NCBI
22	Cui X, Schiff R, Arpino G, Osborne CK and Lee AV: Biology of progesterone receptor loss in breast cancer and its implications for endocrine therapy. J Clin Oncol. 23:7721–7735. 2005. View Article : Google Scholar : PubMed/NCBI
23	Pan H, Gray R, Braybrooke J, Davies C, Taylor C, McGale P, Peto R, Pritchard KI, Bergh J, Dowsett M, et al: 20-Year risks of breast-cancer recurrence after stopping endocrine therapy at 5 Years. N Engl J Med. 377:1836–1846. 2017. View Article : Google Scholar : PubMed/NCBI
24	Breast International Group (BIG) 1–98 Collaborative Group and, ; Thurlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, et al: A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 353:2747–2757. 2005. View Article : Google Scholar : PubMed/NCBI
25	Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M and Forbes JF; ATAC/LATTE investigators, : Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 11:1135–1141. 2010. View Article : Google Scholar : PubMed/NCBI
26	Bevers TB, Helvie M, Bonaccio E, Calhoun KE, Daly MB, Farrar WB, Garber JE, Gray R, Greenberg CC, Greenup R, et al: Breast cancer screening and diagnosis, Version 3.2018, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 16:1362–1389. 2018. View Article : Google Scholar : PubMed/NCBI
27	Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner FL, Walker MG, Watson D, Park T, et al: A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 351:2817–2826. 2004. View Article : Google Scholar : PubMed/NCBI
28	van't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, et al: Gene expression profiling predicts clinical outcome of breast cancer. Nature. 415:530–536. 2002. View Article : Google Scholar : PubMed/NCBI
29	Sestak I, Dowsett M, Zabaglo L, Lopez-Knowles E, Ferree S, Cowens JW and Cuzick J: Factors predicting late recurrence for estrogen receptor-positive breast cancer. J Natl Cancer Inst. 105:1504–1511. 2013. View Article : Google Scholar : PubMed/NCBI
30	Filipits M, Rudas M, Jakesz R, Dubsky P, Fitzal F, Singer CF, Dietze O, Greil R, Jelen A, Sevelda P, et al: A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors. Clin Cancer Res. 17:6012–6020. 2011. View Article : Google Scholar : PubMed/NCBI
31	Buus R, Sestak I, Kronenwett R, Denkert C, Dubsky P, Krappmann K, Scheer M, Petry C, Cuzick J and Dowsett M: Comparison of endopredict and EPclin with oncotype DX recurrence score for prediction of risk of distant recurrence after endocrine therapy. J Natl Cancer Inst. 108:2016. View Article : Google Scholar : PubMed/NCBI
32	Jerevall PL, Ma XJ, Li H, Salunga R, Kesty NC, Erlander MG, Sgroi DC, Holmlund B, Skoog L, Fornander T, et al: Prognostic utility of HOXB13:IL17BR and molecular grade index in early-stage breast cancer patients from the Stockholm trial. Br J Cancer. 104:1762–1769. 2011. View Article : Google Scholar : PubMed/NCBI
33	Dowsett M, Sestak I, Regan MM, Dodson A, Viale G, Thürlimann B, Colleoni M and Cuzick J: Integration of clinical variables for the prediction of late distant recurrence in patients with estrogen receptor-positive breast cancer treated with 5 years of endocrine therapy: CTS5. J Clin Oncol. 36:1941–1948. 2018. View Article : Google Scholar : PubMed/NCBI