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Association of progesterone receptor status with 21-gene recurrence score and survival among patients with estrogen receptor-positive breast cancer

BMC Cancer volume 23, Article number: 330 (2023) Cite this article

Abstract

Background

Progesterone receptor (PR)-negative tumors have been shown to have worse prognosis and were underrepresented in recent trials on patients with estrogen receptor (ER)-positive breast cancer. The role of PR-negative status in the context of 21-gene recurrence score (RS) and nodal staging remains unclear.

Methods

The National Cancer Database (NCDB) was queried for women diagnosed between 2010 and 2017 with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative, pT1-3N0-1a breast cancer. Logistic and Cox multivariable analyses (MVA) were performed to identify association of PR status with high RS (> 25) and overall survival (OS), respectively.

Results

Among 143,828 women, 130,349 (90.6%) and 13,479 (9.4%) patients had PR-positive and PR-negative tumors, respectively. Logistic MVA showed that PR-negative status was associated with higher RS (> 25: aOR 16.15, 95% CI 15.23–17.13). Cox MVA showed that PR-negative status was associated with worse OS (adjusted hazards ratio [aHR] 1.20, 95% CI 1.10–1.31). There was an interaction with nodal staging and chemotherapy (p = 0.049). Subgroup analyses using Cox MVA showed the magnitude of the chemotherapy benefit was greater among those with pN1a, PR-negative tumors than pN1a, PR-positive tumors (PR-positive: aHR 0.57, 95% CI 0.47–0.67; PR-negative: aHR 0.31, 95% CI 0.20–0.47). It was comparable among those with pN0 tumors regardless of PR status (PR-positive: aHR 0.74, 95% CI 0.66–0.82; PR-negative: aHR 0.63, 95% CI 0.51–0.77).

Conclusion

PR-negative tumors were independently correlated with higher RS and were associated with greater OS benefits from chemotherapy for pN1a tumors, but not pN0 tumors.

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Introduction

Among patients with estrogen receptor (ER)-positive, human epidermal growth factor 2 (HER2)-negative breast cancer, progesterone receptor (PR)-negative tumors were shown to have worse prognosis than PR-positive tumors [1,2,3]. PR-negative tumors have been shown to be less likely to respond to endocrine therapy than PR-positive tumors [1, 4, 5], and treatment intensification with adjuvant chemotherapy may improve the outcome of PR-negative tumors [6].

However, PR-negative tumors were underrepresented in recent trials that led to a routine use of 21-gene recurrence score (RS) in clinical practice, and they were only 10.0% and 5.7% of all tumors included in TAILORx and RxPONDER trials, respectively [7, 8]. Findings from these trials may not be generalizable to PR-negative tumors. In addition, a recent guideline by the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) recognized the heterogeneity in the extent of staining for ER and PR status, encouraging them to be further stratified by negative, low positive, and positive based on 1% and 10% cutoffs [9]. The role of PR-negative status in the context of RS and nodal staging remains unclear. We performed an observational cohort study to evaluate the association of PR status with RS and the magnitude of chemotherapy benefit on survival.

Method

This study was approved under the protocol (BDR-131220) by Roswell Park Comprehensive Cancer Center, and follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

Patient selection and variable definition

The National Cancer Database (NCDB) was queried for women diagnosed between 2010 and 2017 with ER-positive, HER2-negative, pT1-3N0-1aM0 breast cancer who underwent surgery and adjuvant endocrine therapy with available RS. If 1% or greater cells stained positively, they were considered PR-positive. Otherwise, they were considered PR-negative. Variables of interest were facility type, age at diagnosis, race, medical insurance, income and education level, Charlson-Deyo Comorbidity Score (CDS), year of diagnosis, histology, tumor grade, T and N staging, recurrence score, progesterone receptor status, lymphovascular space invasion (LVSI), surgery, surgical margin, radiation therapy, and chemotherapy. Age was stratified by above versus below 50 years of age. Education and income levels were determined based on the 2016 American Community Survey data between 2012 and 2016. Such levels were the percentages of adults who did not graduate from high school and the median household income adjusted for 2016 inflation, respectively, in each patient’s zip code in the United States. High versus low neighborhood-level income and education were determined by the median value of 10.9% and $50,353, respectively. All missing values were labeled as unknown. Other variables, such as performance status, type and duration of systemic therapy, toxicity profile, breast cancer-specific mortality, tumor recurrence, were not captured in the NCDB.

Statistical analysis

Our primary endpoint was overall survival (OS), the time interval between diagnosis and the last follow up or death from any cause. Baseline characteristics were evaluated using Fisher exact test and Mann–Whitney U test as appropriate. Logistic multivariable analysis (MVA) was performed based on baseline patient and tumor characteristics to identify variables associated with PR-negative tumors. Kaplan–Meier method, log-rank test, and Cox MVA models including all clinically relevant variables were performed for OS. Crude odds ratio and hazards ratio results were reported using logistic and Cox univariable analysis (UVA). Variables included for logistic and Cox MVA are listed in eTable 1 and eTable 2, respectively. For patients diagnosed in 2017, OS were not captured in the NCDB, and these patients were excluded for OS analysis.

Interaction term analysis was performed to assess any heterogeneous association of PR status and chemotherapy receipt with OS. If the interaction term was significant, subgroup analyses were performed to compare the magnitude of the effect of chemotherapy and PR status. To reduce the selection bias and further evaluate the subgroup analysis results, propensity score matching was performed based on all variables of interest. Matching was performed using nearest neighbor method in a 1:1 ratio without replacements. The standardized differences of all variables were less than 0.1, indicating adequate match with negligible differences between arms [10]. To address immortal time bias, Cox MVA analyses were repeated after excluding patients with post-diagnosis OS of less than 6 months. Additional subgroup analysis was performed among those with RS ≤ 25 by repeating logistic and Cox MVA.

All p values were two-sided, and p values less than 0.05 were considered statistically significant. All analyses were performed using R (version 4.0.3, R Project for Statistical Computing, Vienna, Austria).

Results

A total of 143,828 women (median [interquartile range (IQR)] age, 60 [51–67] years) met our criteria (Table 1). Of these, 130,349 (90.6%) and 13,479 (9.4%) patients had PR-positive and PR-negative tumors, respectively. Median (IQR) follow up was 51.5 months (34.8–71.9).

Table 1 Baseline characteristics
Full size table

Logistic and Cox MVA

Logistic MVA showed that PR-negative status was associated with higher RS (> 25: aOR 16.15, 95% CI 15.23–17.13, p < 0.001; eTable 1 in the Supplement). Cox MVA showed that PR-negative status was associated with worse OS (adjusted hazards ratio [aHR] 1.20, 95% CI 1.10–1.31, p < 0.001; eTable 2 in the Supplement). Consistent crude results were observed using logistic (odds ratio [OR] 14.87, 95% CI 14.07–15.73, p < 0.001) and Cox UVA (hazards ratio [HR] 1.52, 95% CI 1.42–1.62, p < 0.001).

Interaction term and subgroup analyses

There was no interaction of PR status with RS (p = 0.42), chemotherapy receipt (p = 0.30), or nodal staging (p = 0.13). While its three-way interaction with RS and chemotherapy was not statistically significant (p = 0.53), there was an interaction with nodal staging and chemotherapy (p = 0.049). Subgroup analyses using Cox MVA showed the magnitude of the benefit of chemotherapy was greater among those with PR-negative node-positive tumors than PR-positive node-positive tumors, while it was comparable among those with node-negative tumors regardless of PR status (Fig. 1).

Fig. 1
figure 1

Forest plot of overall survival associated with chemotherapy stratified by progesterone receptor status and nodal staging using multivariable Cox regression. Dotted vertical line represents a hazards ratio of 0.66 associated with chemotherapy use for the entire cohort. No.: number of patients; aHR: adjusted hazards ratio; CI: confidence interval; PR: progesterone receptor; chemo: chemotherapy

Full size image

Propensity score matching analysis

To further evaluate such subgroups, propensity score matching was performed between those with versus without chemotherapy stratified by PR status and nodal staging. Similar findings were observed after propensity score matching. The magnitude of chemotherapy benefits was greater for those with node-positive tumors (pN1a, PR-positive: HR 0.61, 95% CI 0.50–0.75, p < 0.001; pN1a, PR-negative: HR 0.23, 95% CI 0.12–0.43, p < 0.001; eTable 3 in the Supplement and Fig. 2) compared to those with node-negative tumors (pN0, PR-positive: HR 0.43, 95% CI 0.37–0.50, p < 0.001; pN0, PR-negative: HR 0.53, 95% CI 0.41–0.69, p < 0.001; eTable 4 in the Supplement and Fig. 2).

Fig. 2
figure 2

Kaplan Meier plots for overall survival associated with chemotherapy stratified by progesterone receptor status and nodal staging after propensity score matching, Red: no chemotherapy; blue: chemotherapy; PR: progesterone receptor; OS: overall survival; HR: hazards ratio; 95% CI: 95% confidence interval; chemo: chemotherapy

Full size image

Subgroup analysis to address immortal time bias

After excluding those with post-diagnosis OS of less than 6 months, PR-negative status remained associated with worse OS (aHR 1.20, 95% CI 1.10–1.31, p < 0.001). Interaction with chemotherapy and nodal staging remained to be statistically significant (p = 0.037) with similar findings on subgroup analyses (pN0, PR-positive: aHR 0.74, 95% CI 0.66–0.83, p < 0.001; pN0, PR-negative: aHR 0.64, 95% CI 0.52–0.79, p < 0.001; pN1a, PR-positive: aHR 0.57, 95% CI 0.48–0.68, p < 0.001; pN1a, PR-negative: aHR 0.31, 95% CI 0.20–0.47, p < 0.001).

Subgroup analysis among those with RS ≤ 25

On logistic MVA, PR-negative status remained statistically significant for its association with RS 16–25 compared to RS ≤ 15 (aOR 4.45, 95% CI 4.21–4.71, p < 0.001). On Cox MVA, however, PR-negative status was no longer associated with OS (aHR 1.07, 95% CI 0.97–1.19, p = 0.18), and interaction term analysis among PR status, chemotherapy use, and nodal staging was not statistically significant (interaction p = 0.64).

Discussion

To our knowledge, this is the largest study based on nationwide oncology database to suggest that PR-negative status was independently correlated with higher RS and worse OS. It also suggested that, even after adjusting for age and RS, PR-negative tumors were associated with greater OS benefits from chemotherapy among patients with pN1a, but not pN0, breast cancer.

The proportion of PR-negative tumors in our study (9.4%) was comparable to the United States population-based study (9.1%) [11] as well as prospective trials including TAILORx (10.0%) and RxPONDER (5.7%) trials [7, 8]. Such observation suggests the overall consistency of PR status in patient population among the hospital registry-based database, the population-based database, and prospective trials. However, such proportions were lower than 23% of tumors being PR-negative reported by the study from the United Kingdom and Ireland. This inconsistency may be in part explained by allowing up to 10% of cells stained positively to be considered as PR-negative tumors [12], as opposed to less than 1% of cells as defined in our study.

Our findings on the PR-negative tumors associated with aggressive tumor biology as suggested by high RS and worse OS are consistent with other studies suggesting worse prognosis and survival outcomes [13,14,15]. Although 5-year survival rates for breast cancer have been improving in the United States, ER-positive breast cancers that are PR-negative still have a significantly lower OS compared to ER- and PR-positive tumors [14, 16, 17]. Patients with ER-positive breast cancers with low or no PR expression also have a greater risk of tumor recurrence [15, 17, 18]. Prior population study has shown that when ER-positive breast cancer recurs, 26% of the tumors will convert from PR-positive to PR-negative status, suggesting that a loss of PR expression is indicative of refractory response to hormone therapy responsiveness and further disease progression [14].

In our study, reasons for PR-negative tumors with greater OS benefits from chemotherapy among node-positive tumors compared to node-negative tumors remain unclear. At the absence of systemic therapy, node-positive tumors have been shown to be more aggressive with higher distant recurrence rates [19]. Although not statistically powered for subgroup analysis, KEYNOTE-522 trial also showed the treatment with pembrolizumab was associated with numerically higher survival outcomes among node-positive tumors compared to node-negative counterparts [20]. Patients with ER-positive, PR-negative tumors had comparable, poor outcomes similar to triple negative tumors [2], and given such tumor biology, treatment intensification with chemotherapy is associated with survival benefits for node-positive tumors.

Limitations of our study include inherent biases due to its retrospective nature. In addition, given the nature of OS as an endpoint, a short median follow-up of 51.5 months, and a lack of tumor recurrence data, the number of events was too low for subgroup analysis especially among patients younger than 50 years of age. Although most patients were non-Hispanic White in our cohort, heterogeneous characteristics seen between patients with PR-positive and PR-negative tumors (Table 1) may be in part due to sociodemographic factors and likely inter-related with one another. Additional analyses were not performed to investigate complex interactions among such variables, since they were beyond the scope of this study. In addition, as shown in our subgroup analysis among those with RS ≤ 25 suggesting a lack of association between PR status and OS, our study was likely underpowered to evaluate whether PR-negative status as an adverse prognostic factor would be valid among subgroups established based on menopausal status, age, and RS cutoffs by TAILORx and RxPONDER trials [7, 8].

Conclusion

Our study suggests that PR-negative status is associated with high RS and worse OS. PR-negative tumors were shown to benefit more from chemotherapy than PR-positive tumors in the node-positive setting. Further investigations are warranted to tailor systemic therapies among PR-negative tumors.

Availability of data and materials

The primary dataset (National Cancer Database) is available publicly for investigators associated with Commission on Cancer-accredited programs through the American College of Surgeons (https://www.facs.org/quality-programs/cancer/ncdb).

References

  1. Arpino G, Weiss H, Lee AV, Schiff R, De Placido S, Osborne CK, Elledge RM. Estrogen receptor-positive, progesterone receptor-negative breast cancer: association with growth factor receptor expression and tamoxifen resistance. J Natl Cancer Inst. 2005;97(17):1254–61.

    Article  CAS  PubMed  Google Scholar 

  2. Bae SY, Kim S, Lee JH, Lee HC, Lee SK, Kil WH, Kim SW, Lee JE, Nam SJ. Poor prognosis of single hormone receptor- positive breast cancer: similar outcome as triple-negative breast cancer. BMC Cancer. 2015;15:138.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Li Y, Yang D, Yin X, Zhang X, Huang J, Wu Y, Wang M, Yi Z, Li H, Li H, Ren G. Clinicopathological Characteristics and Breast Cancer-Specific Survival of Patients With Single Hormone Receptor-Positive Breast Cancer. JAMA Netw Open. 2020;3(1): e1918160.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Cui X, Schiff R, Arpino G, Osborne CK, Lee AV. Biology of progesterone receptor loss in breast cancer and its implications for endocrine therapy. J Clin Oncol. 2005;23(30):7721–35.

    Article  CAS  PubMed  Google Scholar 

  5. Rakha EA, El-Sayed ME, Green AR, Paish EC, Powe DG, Gee J, Nicholson RI, Lee AH, Robertson JF, Ellis IO. Biologic and clinical characteristics of breast cancer with single hormone receptor positive phenotype. J Clin Oncol. 2007;25(30):4772–8.

    Article  PubMed  Google Scholar 

  6. van der Hage JA, Mieog JS, van de Vijver MJ, van de Velde CJR. European Organization for, and C. Treatment of, Efficacy of adjuvant chemotherapy according to hormone receptor status in young patients with breast cancer: a pooled analysis. Breast Cancer Res. 2007;9(5):R70.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Kalinsky K, Barlow WE, Gralow JR, Meric-Bernstam F, Albain KS, Hayes DF, Lin NU, Perez EA, Goldstein LJ, Chia SKL, Dhesy-Thind S, Rastogi P, Alba E, Delaloge S, Martin M, Kelly CM, Ruiz-Borrego M, Gil-Gil M, Arce-Salinas CH, Brain EGC, Lee ES, Pierga JY, Bermejo B, Ramos-Vazquez M, Jung KH, Ferrero JM, Schott AF, Shak S, Sharma P, Lew DL, Miao J, Tripathy D, Pusztai L, Hortobagyi GN. 21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer. N Engl J Med. 2021;385(25):2336–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sparano J.A, Gray R.J, Makower D.F, Pritchard K.I, Albain K.S, Hayes D.F, Geyer C.E Jr., Dees E.C, Goetz M.P, Olson J.A Jr, Lively T, Badve S.S, Saphner T.J, Wagner L.I, Whelan T.J, Ellis M.J, Paik S, Wood W.C, Ravdin P.M, Keane M.M, Gomez Moreno H.L, Reddy P.S, Goggins T.F, Mayer I.A, Brufsky A.M, Toppmeyer D.L, Kaklamani V.G, Berenberg J.L, Abrams J, Sledge G.W Jr. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. N Engl J Med. 2018;379(2):111–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Allison KH, Hammond MEH, Dowsett M, McKernin SE, Carey LA, Fitzgibbons PL, Hayes DF, Lakhani SR, Chavez-MacGregor M, Perlmutter J, Perou CM, Regan MM, Rimm DL, Symmans WF, Torlakovic EE, Varella L, Viale G, Weisberg TF, McShane LM, Wolff AC. Estrogen and Progesterone Receptor Testing in Breast Cancer: ASCO/CAP Guideline Update. J Clin Oncol. 2020;38(12):1346–66.

    Article  PubMed  Google Scholar 

  10. Haukoos JS, Lewis RJ. The Propensity Score. JAMA. 2015;314(15):1637–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hoskins KF, Danciu OC, Ko NY, Calip GS. Association of Race/Ethnicity and the 21-Gene Recurrence Score With Breast Cancer-Specific Mortality Among US Women. JAMA Oncol. 2021;7(3):370–8.

    Article  PubMed  Google Scholar 

  12. Dodson A, Parry S, Ibrahim M, Bartlett JM, Pinder S, Dowsett M, Miller K. Breast cancer biomarkers in clinical testing: analysis of a UK national external quality assessment scheme for immunocytochemistry and in situ hybridisation database containing results from 199 300 patients. J Pathol Clin Res. 2018;4(4):262–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Boland MR, Ryan ÉJ, Dunne E, Aherne TM, Bhatt NR, Lowery AJ. Meta-analysis of the impact of progesterone receptor status on oncological outcomes in oestrogen receptor-positive breast cancer. Br J Surg. 2019;107(1):33–43.

    Article  PubMed  Google Scholar 

  14. Purdie CA, Quinlan P, Jordan LB, Ashfield A, Ogston S, Dewar JA, Thompson AM. Progesterone receptor expression is an independent prognostic variable in early breast cancer: a population-based study. Br J Cancer. 2014;110(3):565–72.

    Article  CAS  PubMed  Google Scholar 

  15. Van Asten K, Slembrouck L, Olbrecht S, Jongen L, Brouckaert O, Wildiers H, Floris G, Van Limbergen E, Weltens C, Smeets A, Paridaens R, Giobbie-Hurder A, Regan MM, Viale G, Thürlimann B, Vergote I, Christodoulou E, Van Calster B, Neven P. Prognostic Value of the Progesterone Receptor by Subtype in Patients with Estrogen Receptor-Positive, HER-2 Negative Breast Cancer. Oncologist. 2019;24(2):165–71.

    Article  PubMed  Google Scholar 

  16. Chen L, Linden HM, Anderson BO, Li CI. Trends in 5-year survival rates among breast cancer patients by hormone receptor status and stage. Breast Cancer Res Treat. 2014;147(3):609–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Creighton CJ, Kent Osborne CV, van de Vijver MJ, Foekens JA, Klijn JG, Horlings HM, Nuyten D, Wang Y, Zhang Y, Chamness GC, Hilsenbeck SG. Molecular profiles of progesterone receptor loss in human breast tumors. Breast cancer research and treatment. 2009;114:287–99.

    Article  CAS  PubMed  Google Scholar 

  18. Chaudhary LN, Jawa Z, Szabo A, Visotcky A, Chitambar CR. Relevance of progesterone receptor immunohistochemical staining to Oncotype DX recurrence score. Hematol Oncol Stem Cell Ther. 2016;9(2):48–54.

    Article  CAS  PubMed  Google Scholar 

  19. Pan H, Gray R, Braybrooke J, Davies C, Taylor C, McGale P, Peto R, Pritchard KI, Bergh J, Dowsett M, Hayes DF, Ebctcg. 20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years. N Engl J Med. 2017;377(19):1836–46.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Schmid P, Cortes J, Dent R, Pusztai L, McArthur H, Kummel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Untch M, Fasching PA, Cardoso F, Andersen J, Patt D, Danso M, Ferreira M, Mouret-Reynier MA, Im SA, Ahn JH, Gion M, Baron-Hay S, Boileau JF, Ding Y, Tryfonidis K, Aktan G, Karantza V, O’Shaughnessy J, K.-. Investigators. Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer. N Engl J Med. 2022;386(6):556–67.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

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From National Cancer Database Terms of Agreement:

“The National Cancer Database (NCDB) is a joint project of the Commission on Cancer (CoC) of the American College of Surgeons and the American Cancer Society. The CoC's NCDB and the hospitals participating in the CoC NCDB are the source of the de-identified data used herein; they have not verified and are not responsible for the statistical validity of the data analysis or the conclusions derived by the authors.”

Funding

This research was supported by the National Cancer Institute Cancer Center Support Grant (P30CA016056). Sponsors had no role in the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, 665 Elm Street, Buffalo, NY, 14203, USA

    Sung Jun Ma, Udit Chatterjee, Fatemeh Fekrmandi, Rohil Shekher, Austin Iovoli & Anurag K. Singh

  2. University at Buffalo, The State University of New York 12 Capen Hall, Buffalo, NY, 14260, USA

    Jasmin Gill & Keerti Yendamuri

  3. Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, 955 Main Street, Buffalo, NY, 14203, USA

    Olivia Waldman & Cynthia Dunne-Jaffe

  4. Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, 665 Elm Street, Buffalo, NY, 14203, USA

    Song Yao

  5. Department of Radiation Oncology, University of Florida, 2000 SW Archer Road, Gainesville, FL, 32608, USA

    Oluwadamilola T. Oladeru

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Contributions

S.M. designed and analyzed the study. S.M., J.G., K.Y., U.C., O.W., and C.D wrote the main manuscript text. All authors revised the manuscript critically, provided the interpretation of the data, and reviewed the manuscript. S.Y., O.O., and A.S. provided the supervision of this study. The author(s) read and approved the final manuscript.

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Correspondence to Anurag K. Singh.

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Ethics approval and consent to participate

The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). Our study was approved by Roswell Park Comprehensive Cancer Center institutional review board (BDR-131220). A waiver of consent was obtained from the Institutional Review Board of Roswell Park Comprehensive Cancer Center due to the retrospective nature of the study based on the publicly available, deidentified dataset making consent impractical and contacting patients to obtain consent would pose a greater risk than the waiver.

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All authors declare that they have no competing interests.

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Supplementary Information

Additional file 1: eTable 1.

Logistic multivariable analysis for progesterone receptor status. eTable 2. Cox multivariable analysis for overall survival. eTable 3. Baseline characteristics for node-positive tumors after propensity score matching. eTable 4. Baseline characteristics for node-negative tumors after propensity score matching. 

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Ma, S.J., Gill, J., Yendamuri, K. et al. Association of progesterone receptor status with 21-gene recurrence score and survival among patients with estrogen receptor-positive breast cancer. BMC Cancer 23, 330 (2023). https://doi.org/10.1186/s12885-023-10796-4

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