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Article

Are All Prognostic Stage IB Breast Cancers Equivalent? †

by
Stephanie M. Yoon
1,
Shengyang Wu
2,
Amanda Schwer
3,
Scott Glaser
1,
Todd DeWees
1 and
Jose G. Bazan
1,*
1
Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA 91010, USA
2
City of Hope Arcadia Radiation Oncology, Arcadia, CA 91007, USA
3
Department of Radiation Oncology, City of Hope Orange County Lennar Foundation Cancer Center, Irvine, CA 92618, USA
*
Author to whom correspondence should be addressed.
†
This paper is presented at the Proceedings of the American Society of Radiation Oncology, San Diego, CA, USA, 1 October 2023.
Cancers 2024, 16(22), 3830; https://doi.org/10.3390/cancers16223830
Submission received: 17 October 2024 / Revised: 7 November 2024 / Accepted: 12 November 2024 / Published: 14 November 2024
(This article belongs to the Special Issue Breast Cancer: Biomarkers of Diagnosis and Prognosis)
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Review Reports Versions Notes

Simple Summary

Pathologic prognostic stage IB breast cancer is heterogeneous. It includes hormone-positive/HER2-negative (HR+/HER2-) breast cancers that have spread to nearby tissues or lymph nodes to small (<2 cm) early-stage triple-negative breast cancer (TNBC). However, prior studies demonstrated that disease involvement in regional lymph nodes is a key factor in prognosis and risk for disease recurrence. The discordance between anatomic and prognostic stages presents a challenge in recommending personalized treatments. Therefore, we studied women with extreme ranges of anatomic staging and biomarker status within this prognostic stage: locally advanced (HR+/HER2-; pT3N1 or pT1-3N2, grade 1–2) and node-negative early-stage TNBC (T1N0, grade 2–3) in the National Cancer Database to better understand survival differences between these groups. We found that patients with LA-HR+/HER2- BC have significantly worse survival compared to those with ES-TNBC, despite both being classified as pathologic prognostic stage IB cancers and receiving all appropriate treatments. Our study findings indicate a need to improve breast cancer prognostic staging for more accurate survival predictions.

Abstract

Background/Objectives: The 8th edition of the American Joint Committee on Cancer integrates histology and biomarker status with anatomic extent in breast cancer (BC) pathologic prognostic staging (PPS). However, PPS IB includes anatomic locally advanced hormone-receptor-positive/HER2-negative (LA-HR+/HER2-) and early-stage triple-negative BC (ES-TNBC). Previous research shows that increased nodal involvement is a critical predictor of worse prognosis, raising questions about whether biological subtype or anatomic stage has a greater influence on outcomes in these discordant cases. We hypothesized that overall survival (OS) remains worse for LA-HR+/HER2- BC compared to ES-TNBC, despite both being classified as PPS IB. Methods: Using the National Cancer Database, we identified patients with LA-HR+/HER2- BC (pT3N1 or pT1-3N2, grade 1–2) and ES-TNBC (T1N0, grade 2–3) treated between 2004 and 2017. Patients without complete primary tumor stage, biomarker status, grade, TNM staging, or treated with neoadjuvant therapy were excluded. The primary endpoint was OS. Multivariable Cox regression evaluated OS between LA-HR+/HER2- BC and ES-TNBC. Results: Among 45,818 patients (17,359 LA-HR+/HER2- BC and 28,459 ES-TNBC), LA-HR+/HER2- BC had significantly worse 6-year OS (86.1% vs. 90.4%; HR = 1.63; p < 0.0001). Among patients receiving appropriate therapies, patients with LA-HR+/HER2- BC had 35% relatively higher risk of death (HR = 1.35; 1.24–1.48; p < 0.0001). These results highlight that LA-HR+/HER2- breast cancer has worse survival compared to ES-TNBC, despite both being classified as PPS IB and receiving all appropriate treatments. Conclusions: Anatomic disease extent remains an important factor in patients with discordant AS and PPS. Future iterations of PPS should re-classify LA-HR+/HER2- breast cancer from PPS IB to ensure more accurate prognostic and survival information.

1. Introduction

Breast cancer (BC) is a highly heterogeneous entity, and significant progress has been made in understanding its complex clinical and biological characteristics. Histopathologic grade and biomarker status have been highly related to prognosis [1,2,3,4,5,6,7]. It is now standard for clinicians to tailor therapeutic recommendations based on biologic subtype, thus ushering in an era of personalized therapy. For a long time, breast cancer was staged based on anatomic extent of disease, but the American Joint Committee on Cancer (AJCC) recently recognized the prognostic influence of histologic and biologic variants in its 8th edition cancer staging manual [8].
The new pathologic prognostic staging (PPS) for BC is now applied for all patients undergoing surgical resection as their initial treatment prior to receipt of radiation or systemic therapy. PPS integrates both anatomic disease extent and biological factors, including tumor grade, biomarker status (hormone receptor [HR] status that includes expression of estrogen receptors [ERs] and/or progesterone receptors [PRs] on the surface of tumor cells), human epidermal receptor 2 (HER2) amplification status, and multigene assay results. However, PPS IB remains heterogeneous and includes a wide range of patients from locally advanced anatomic pathologic stage IIIA/B (pT3N1 or pT1-3N2, G1–2) HR-positive/HER2-negative BC (LA-HR+/HER2- BC) to those with early-stage anatomic pathologic stage IA (T1N0, G2–3) triple-negative BC (ES-TNBC). This wide range of disease characteristics creates a discordance between anatomic disease extent and tumor biology. Generally, node-positive BC is linked to a higher risk of distant recurrences and poorer prognosis compared to node-negative BC [9,10,11]. The inclusion of LA-HR+/HER2- BC in the same prognostic stage as those with node-negative, small (under 2 cm) TNBC has raised concerns among patients. There is a dilemma as to which factor—tumor biology or anatomical disease extent—has greater importance in prognosis to guide treatment recommendations [12,13].
Scarce data are available as to whether biologic subtype or anatomic staging (AS) have greater prognostic impact on clinical outcomes in such discordant situations. The primary objective of this study is to evaluate the clinical outcomes of PPS IB breast cancer in greater detail. We focus on patients at the extremes of both AS and bioreceptor status within PPS IB, as defined by AJCC 8th edition staging manual. Specifically, we examined OS in patients with LA-HR+/HER2- BC and those with ES-TNBC. We hypothesize that OS will be worse for patients with LA-HR+/HER2- BC compared to those with ES-TNBC, despite both groups being classified as PPS IB.

2. Materials and Methods

This retrospective cohort study was reviewed and approved by the institutional review board at City of Hope National Medical Center with an exemption for informed consent requirements due to use and analysis of deidentified patient data. Data were sourced from the National Cancer Database (NCDB), a publicly available, hospital-based database collected over 1500 accredited facilities by the American College of Surgeons Commission on Cancer [14]. NCDB captures approximately 75% of newly diagnosed cancers in the United States.
We identified adult patients (≥18 years old) with surgically resected pT3N1 or pT1-3N2, grade 1–2 locally advanced HR+/HER2- BC (LA-HR+/HER2-) and those with T1N0, grade 2–3 ES-TNBC from 2004 to 2017. We excluded patients with unknown values for the following variables since these are necessary for AS and PPS: primary tumor stage, HR and HER2 status, tumor grade, and/or pathologic TNM staging data. To maintain consistency in treatments across the cohort, we also excluded missing treatment information, as well as HR+/HER2- patients treated with neoadjuvant therapy since most patients with luminal A tumors do not typically undergo this treatment and the prognostic pathologic stage may be influenced by neoadjuvant therapy.
The study cohort was characterized using descriptive statistics. The primary endpoint was OS, which was estimated using the Kaplan–Meier method. OS was calculated from the date of diagnosis to the date of death or last follow-up. Log-rank test assessed for differences in OS between anatomic LA-HR+/HER2- BC and ES-TNBC (adjusting for baseline patient demographic characteristics). Survival analysis was performed in the entire cohort and in the subset of patients receiving all appropriate treatment based on AS: (1) radiation (RT), chemotherapy (CT), and hormone therapy for LA-HR+/HER2- BC and (2) CT or CT+RT for ES-TNBC treated with mastectomy or lumpectomy, respectively. We used multivariable Cox regression analysis to evaluate the association of BC subtype and AS with OS among the subset of patients who received all appropriate treatments. The primary predictor variable was anatomic BC stage: LA-HR+/HER2- BC or ES-TNBC. Covariables potentially impacting OS were included in the analysis: age (<40, 40–49, 50–59, 60–69, ≥70 years old), medical comorbidities (Charlson–Deyo Score 0 vs. ≥ 1, race/ethnicity (White, Black, Hispanic, Asian, Other, Unknown), surrogates for socioeconomic factors (insurance status [private, government, uninsured, unknown], median income [<USD 63,000, ≥USD 63,000, unknown], education [high-school diploma < 13.0%, ≥13.0%, unknown], and treatment facility type (academic, other, unknown). Further, given that the hazard ratio (HR) for recurrence over time appears non-proportional for TNBC but remains relatively constant for HR+/HER2- BC, we hypothesized that the HR for OS between the two groups could vary with time [15]. We implemented landmark analyses every 3 months, choosing the optimal landmark based on the time at which the adjusted hazard ratio for OS demonstrated a peak followed by a plateauing effect. We report hazard ratios with 95% confidence intervals (CIs) with p < 0.05 considered statistically significant.

3. Results

We included a total of 45,818 patients with PPS IB treated between 2004 and 2017 that met the inclusion criteria: 17,359 patients had LA-HR+/HER2- BC and 28,459 had ES-TNBC. CONSORT diagram for included patients is found in Figure S1, and patient demographics are summarized in Table 1. Notably, 77.9% of patients were ≥ 50 years, and 82.6% had no associated comorbidities. Of patients with LA-HR+/HER2- BC, 13,064 (75.3%) had AS pT1-3N2 disease while the remaining had pT3N1 disease. Table 2 summarizes treatment delivery by AS groups. Approximately two-third of patients in each group received appropriate treatment based on AS: 11,533 (66.4%) patients with LA-HR+/HER2- BC and 19,512 (69.6%) with ES-TNBC.
Median follow-up for the entire cohort was 56.3 months (IQR = 35.8–80.9 months). Six-year OS rates were 86.1% (LA-HR+/HER2- BC) vs. 90.4% (ES-TNBC). Compared to patients with ES-TNBC, patients with LA-HR+/HER2- BC had a 63% relative increased risk of death after adjusting for all covariates (HR = 1.63; 95% CI 1.53–1.73; p < 0.0001) (Figure 1a). In addition, Table S1 shows that age ≥ 70 years having ≥ 1 medical comorbidity, ethnoracial category, insurance status, income, and facility type were all significantly associated with OS.
In the 31,045 patients that received appropriate treatment, the median follow-up was 58.7 months (IQR = 37.9–83.0 months). Six-year OS was 91.8% (LA-HR+/HER2- BC) vs. 93.3% (ES-TNBC). Patients with LA-HR+/HER2- BC had a 35% increased risk of death (HR = 1.35; 95% CI 1.24–1.48; p < 0.0001) compared to those with ES-TNBC after adjusting for all covariates (Figure 1b). Findings from Cox regression are summarized in Table 3.

Landmark Analysis

As demonstrated in Figure 1, absolute 5-year OS was worse amongst patients with LA-HR+/HER2- BC in the entire cohort (89.4% vs. 92.2%) and essentially identical in those receiving appropriate treatment (94.2% vs. 94.5%). As we hypothesized, Figure S2 demonstrates the HR for OS between the LA-HR+/HER2- BC and ES-TNBC groups varied significantly as a function of time. At 54 months, there was a sharp increase in the HR. We therefore chose 54 months as the cut point for the landmark analysis. In the entire cohort, there were 24,057 patients (N = 14,966 ES-TNBC; N = 9091 HR+/HER2- BC) with a follow-up of ≥ 54 months (median = 79.5 months; IQR = 65.8–95.9 months) and a total of 1510 events. The adjusted HR for OS was 2.26 (95% CI = 2.04–2.50) with full results for the multivariable analysis in Table S2. In the subgroup of patients who received all appropriate treatments, there were 17,112 patients (N = 10,591 ES-TNBC; N = 6521 HR+/HER2- BC) with ≥ 54 months of follow-up (median = 80 months, IQR = 66.0–96.3 months) and 751 events. Table 4 shows that the adjusted HR for OS was similar to that of the entire cohort with a value of 2.30 (95% CI = 1.99–2.66). The corresponding 7-year OS was 96.7% in patients with ES-TNBC vs. 93.2% in patients with LA-HR+/HER2- BC (Figure 2).

4. Discussion

In this study, we took the most extreme groups of patients that fall within prognostic stage IB breast cancer—those with anatomic pathologic stage IIIA-B (pT3N1 or pT1-3N1, grade 1–2 HR+/HER2- BC) and those with T1N0, G2–3 TNBC. Our goal was to evaluate OS and determine if clinical outcomes truly differ between these groups. We found that the OS was not the same between ES-TNBC (T1N0, grade 2–3) and LA-HR+/HER2- BC (pT3N1 or pT1-3N2, grade 1–2). Specifically, we found that patients with LA-HR+/HER2- BC have worse OS, and this OS difference persisted even when we restricted the analysis to patients who received appropriate oncologic treatment based on their AS of disease. These findings suggest that pathologic lymph node involvement should not be overlooked in HR+/HER2- BC. The current PPS should not include pT3N1 or pT1-3N2, grade 1–2 HR+/HER2- BC as PPS IB based on this evidence.
Breast cancer is a highly heterogeneous disease. Advances in genomic and molecular profiling have allowed clinicians to consider several other factors when tailoring treatment plans and predicting outcomes more accurately. Briefly, HR-positive BC generally has a more favorable prognosis compared to HR-negative BC or TNBC. This subtype has a slower growth trajectory and lower (though prolonged) incidence for relapse, which provide opportunities to intervene with effective treatments like endocrine therapies [6,16,17,18,19]. HER2-positive BC initially was associated with poor outcomes, but with routine use of anti-HER2-directed therapies, this subtype now has better prognosis [17,20,21,22]. TNBC is associated with worse prognosis due to its propensity for higher early disease relapse and lack of effective therapies leading to early death [4,5,23,24]. Histologic grade also has been demonstrated to have impact on BC prognosis [25,26]. Therefore, BC prognosis is no longer solely based on anatomic disease extent, and the AJCC 8th edition staging manual confirmed the value of biologic factors in predicting prognosis.
PPS has been externally validated across several institutions [13,21,27,28,29,30,31,32,33,34]. These studies have consistently shown improved discriminatory power over AS which confirmed its use in routine clinical practice. Weiss et al. compared disease-specific survival (DSS) according to AS and PPS across two cohorts of patients identified from a single institution and a large population database [27]. They reported that PPS provided more accurate DSS stratification compared to its associated AS (C-index = 0.737; p > 0.001) among the 3327 patients with stage I-III BC identified at the MD Anderson Cancer Center (MDACC) treated between 2007 and 2013. Similar results were found after assessing 54,727 patients with stage I-IV BC from 2005 to 2009 in the California Cancer Registry (C-index = 0.842; p < 0.001). However, most of these studies cross-validated PPS with the same AS. PPS upstaged 29.5% and 31.0% of patients in the MDACC and California Cancer registry cohorts, respectively, while it downstaged 28.1% and 20.6% of patients. Validation on non-metastatic patients identified in the surveillance, epidemiology, and end results (SEER) database also confirmed improved discriminatory ability in predicting BC-specific mortality, with C-statistic of 0.767 (95% CI = 0.759–0.776) with AS and 0.814 (95% CI = 0.807–0.822) with PS [21]. This study also performed stepwise pair comparisons between stages and found significant differences between stages (p < 0.05). Most other validation studies have compared PPS with its associated AS or within a specific BC subtype.
However, PPS categorizes a wide range of AS from various molecular subtypes into the same prognostic stage. Currently, PPS IB encompasses a range of patients from early-stage anatomic clinical/pathologic stage IA TNBC to LA-HR+/HER2- BC. The discordance between AS, particularly for LA-HR+/HER2- BC, with prognostic stage presents a clinical challenge in recommending personalized treatments especially since prior studies demonstrated greater nodal involvement is a key determinant in prognosis and is significantly associated with an increased risk for disease recurrence [35,36]. In this study, we found that LA-HR+/HER2- BC has significantly worse OS compared to node-negative ES-TNBC despite both being classified as prognostic stage IB and accounting for treatments delivered. Worsened survival was more evident ~4–5 years after treatment.
Two SEER 18 database studies have confirmed the improved performance of PPS over AS within LA-HR+/HER2- BC and TNBC patient populations. Wang et al. specifically compared PPS to AS among 10,053 patients with LABC in the SEER 18 database from 2010 to 2013 [32]. They found that 57.1% of cases with LA-HR+/HER2- BC were downstaged, while 60.4% of cases with grade 3 and 68.3% of cases with locally advanced TNBC were upstaged. PPS remains a significant independent prognostic factor for OS on multivariable analysis. When patients were stratified based on PPS, there was no significant difference in DSS for prognostic stage IB-IIIA but was significantly different compared to prognostic stage IIIB-IIIC. Specific pairwise comparison between prognostic stage IB to IIIA also did not have significantly different DSS. This study highlights that hormone receptor status in LABC may carry similar prognosis as early-stage BC [37]. Molecular status may have greater prognostic impact in predicting clinical outcomes for patients with discordant anatomic disease extent and biologic subtypes such as LA-HR+/HER2- BC. Another study led by Luo et al. validated PPS for patients in the SEER 18 database with TNBC treated from 2010 to 2015 [13]. They found that more than half of patients were upstaged based on PPS and no cases were downstaged. The performance of PPS outperformed AS among this patient population. Interestingly, they found that when different AS were distributed to the same prognostic stage, and there were significant differences in survival curves, which suggest that anatomic disease extent remains a relatively important factor to consider for TNBC.
Anatomic extent of disease is an extremely important prognostic marker for patients to know, yet even in an era before prognostic staging was developed, data demonstrate that patients have poor understanding of the meaning of stage [38]. Patients need to know their stage of disease not only to guide prognosis but also to aid in treatment decision making as patients often express that the treatment they receive for their cancer should be in line with the severity of the disease [39]. We recognize PPS IB encompasses a wide range of AS; yet we purposely included patients with LA-HR+/HER2- breast cancer in this study because the most striking difference is present between AS (IIIA/B) and PPS (IB) for these patients. The 8th edition of the AJCC staging manual clearly states that, in patients that undergo upfront surgery and in countries where all prognostic variables are captured, PPS should be documented in the patient’s record. The staging manual also specifies that PPS is only accurate in patient’s that receive appropriate therapy for their anatomic extent of disease and biomarker status and even states that “lower stage does not denote the need for less treatment” [40]. In clinical practice, these subtle but important details need to be explained to patients, particularly those with pT3-1pN1-2 ER+/HER2-, grade 1–2 disease, such that they understand that while the medical record classifies them as having stage IB disease, they still need to complete all adjuvant therapy, including not only chemotherapy and radiation, but also endocrine therapy. We note that a slightly higher proportion of patients in our cohort with ES-TNBC (69%) completed all appropriate treatments compared to patients with LA-HR+/HER2- BC (66%), which potentially may impact clinical outcomes. However, evaluating OS as the primary endpoint may mitigate any inherent bias in this retrospective review.
However, the key result from this study is that, even with appropriate treatment, the prognosis of patients with PPS IB LA HR+/HER2- BC appears to be worse compared to patients with PPS IB (T1c N0, G2–3) ES-TNBC. While the absolute differences in OS were small early in the study period, we undertook a landmark analysis with an a priori knowledge that recurrence rates are not proportional between TNBC and HR+/HER2- breast cancer. As demonstrated by Hilsenbeck et al., the risk of recurrence in patients with TNBC peaks sharply within the first 2–3 years of diagnosis and then declines to nearly 0, while the risk of recurrence in HR+/HER2- disease remains low but constant over time. Therefore, we see a divergence in the OS curves between the two groups we studied that begins at about 4 years and widens over time consistent with the natural history of HR+/HER2- disease. All of the patients with LA-HR+/HER2- breast cancer would have likely benefited from extended endocrine therapy as well as adjuvant cyclin-dependent kinase 4/6 inhibitors, though it is likely that many of the patients did not receive these treatments in the given study period [35,41,42]. With this in mind, it is possible that, if patients receive optimal adjuvant systemic therapy that is the standard of care today, the OS differences between LA HR+/HER2- BC and ES-TNBC may dissipate, but this can only be confirmed in future iterations of the NCDB that includes more patients treated in this manner.
To our knowledge, no studies have compared different AS and molecular subtype combinations within the same PPS. A Korean retrospective study performed prior to the establishment of PPS highlighted the prognostic importance of BC molecular subtypes by demonstrating that advanced AS (II-III) HR+/HER2- BC had better recurrence-free survival and OS compared to AS I, unfavorable histology (HER2+ or TN) BC [12]. Five-year recurrence-free survival was 99% vs 92%, respectively (p < 0.011), while five-year OS was 99% vs 96%, respectively (p = 0.03). While 5-year OS was similar to those found in our study, their conclusions contradicted our findings. This may be potentially due to several reasons including inclusion of AS II HR+/HER2- BC as an advanced stage, which could lead to better than expected OS compared to those with strictly AS III disease, and inclusion of HER2+ disease in AS I, unfavorable histology comparison group, which may also increase OS and/or recurrence-free survival rates compared to TNBC since over two-thirds of patients with HER2+ disease received anti-HER2-directed therapy, which has shown to improve clinical outcomes. We also recognize that the OS differences in our study were evident after 5 years.
Overall, while evidence in the literature have demonstrated that LA-HR+/HER2- BC has very favorable clinical outcomes, our study highlights that anatomic disease extent remains important to consider in sub-population of patients with discordant AS and PPS [43]. Our findings suggest the current PPS needs further refinement and should not include LA-HR+/HER2- as PPS IB. Considering ~60–80% of all BC is HR+ with 90% of these staged as AS I-III, it is important to further clarify relevant biologic and anatomic factors that define disease at high risk for death or recurrence [44,45].
Our study has several limitations related to its retrospective nature and use of NCDB data for analysis [46]. First, the NCDB reports death from any cause; thus, it is possible our findings may differ if disease-specific deaths due to BC were considered. Second, the exact systemic therapy regimens and duration, particularly with respect to endocrine therapy, are not available in the NCDB. This study is hypothesis-generating, and our findings need further validation in independent cohorts of patients.

5. Conclusions

The AJCC 8th edition prognostic stage offers an advancement over anatomic staging alone by providing improved prognostic insights for breast cancer. However, our study indicates that classifying LA-HR+/HER2- BC (pT3N1 or pT1-3N2, G1–2) as pathologic prognostic stage IB inaccurately represents the actual prognosis for this group. A revised classification would provide patients with a more precise understanding of their expected overall survival, enabling more tailored clinical decisions. In the meantime, it is important for clinicians to convey these subtle but critical distinctions to patients and stress the importance of adhering to all recommended adjuvant therapy for optimal outcomes.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/cancers16223830/s1, Figure S1: CONSORT Diagram; Figure S2: Landmark analysis demonstrating change in hazard ratio over time (months) for the entire cohort; Table S1: Multivariable analysis for entire cohort, regardless of treatment; Table S2: Multivariable analysis for entire cohort included in the landmark analysis.

Author Contributions

Conceptualization, J.G.B.; methodology, J.G.B.; data curation, S.M.Y. and J.G.B.; formal analysis, T.D. and J.G.B.; writing—original draft preparation, S.M.Y. and J.G.B. writing—review and editing, S.Y, S.W., A.S. and S.G.; supervision, J.G.B. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

This study did not require institutional review board approval as we used de-identified patient information from the National Cancer Database for our study. The study is retrospective and was conducted according to the guidelines published by the National Cancer Database.

Informed Consent Statement

Patient consent was waived due to use of only de-identified information from the National Cancer Database.

Data Availability Statement

Data cannot be provided by authors of this study as data were derived from the National Cancer Database (NCDB). Data can be requested directly from the NCDB.

Conflicts of Interest

J.B. has received research support from Intraop Medical and GE Healthcare. J.B. receives honoraria for panel work with American Society for Radiation Oncology. All other authors declare no conflicts of interest.

References

  1. Slamon, D.J. Studies of the HER-2/neu proto-oncogene in human breast cancer. Cancer Investig. 1990, 8, 253–254. [Google Scholar] [CrossRef] [PubMed]
  2. Perou, C.M.; Sørlie, T.; Eisen, M.B.; Van De Rijn, M.; Jeffrey, S.S.; Rees, C.A.; Pollack, J.R.; Ross, D.T.; Johnsen, H.; Akslen, L.A. Molecular portraits of human breast tumours. Nature 2000, 406, 747–752. [Google Scholar] [CrossRef] [PubMed]
  3. Rakha, E.A.; El-Sayed, M.E.; Lee, A.H.; Elston, C.W.; Grainge, M.J.; Hodi, Z.; Blamey, R.W.; Ellis, I.O. Prognostic significance of Nottingham histologic grade in invasive breast carcinoma. J. Clin. Oncol. 2008, 26, 3153–3158. [Google Scholar] [CrossRef] [PubMed]
  4. Dent, R.; Hanna, W.M.; Trudeau, M.; Rawlinson, E.; Sun, P.; Narod, S.A. Pattern of metastatic spread in triple-negative breast cancer. Breast Cancer Res. Treat. 2009, 115, 423–428. [Google Scholar] [CrossRef]
  5. Choi, J.; Jung, W.-H.; Koo, J.S. Clinicopathologic Features of Molecular Subtypes of Triple Negative Breast Cancer Based on Immunohistochemical Markers. Histol. Histopathol. 2012, 27, 1481–1493. [Google Scholar] [CrossRef]
  6. Sun, Y.; Nie, G.; Wei, Z.; Lv, Z.; Liu, X.; Wang, H. Luminal breast cancer classification according to proliferative indices: Clinicopathological characteristics and short-term survival analysis. Med. Oncol. 2014, 31, 55. [Google Scholar] [CrossRef]
  7. Nicolini, A.; Ferrari, P.; Duffy, M.J. Prognostic and predictive biomarkers in breast cancer: Past, present and future. In Seminars in Cancer Biology; Elsevier: Amsterdam, The Netherlands, 2018; Volume 52, pp. 56–73. [Google Scholar]
  8. Amin, M.B.; Greene, F.L.; Edge, S.B.; Compton, C.C.; Gershenwald, J.E.; Brookland, R.K.; Meyer, L.; Gress, D.M.; Byrd, D.R.; Winchester, D.P. The eighth edition AJCC cancer staging manual: Continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J. Clin. 2017, 67, 93–99. [Google Scholar] [CrossRef]
  9. Veronesi, U.; Marubini, E.; Vecchio, M.D.; Manzari, A.; Andreola, S.; Greco, M.; Luini, A.; Merson, M.; Saccozzi, R.; Rilke, F. Local recurrences and distant metastases after conservative breast cancer treatments: Partly independent events. JNCI J. Natl. Cancer Inst. 1995, 87, 19–27. [Google Scholar] [CrossRef]
  10. Engel, J.; Eckel, R.; Aydemir, Ü.; Aydemir, S.; Kerr, J.; Schlesinger-Raab, A.; Dirschedl, P.; Hölzel, D. Determinants and prognoses of locoregional and distant progression in breast cancer. Int. J. Radiat. Oncol. 2003, 55, 1186–1195. [Google Scholar] [CrossRef]
  11. Kay, C.; Martinez-Perez, C.; Dixon, J.M.; Turnbull, A.K. The Role of Nodes and Nodal Assessment in Diagnosis, Treatment and Prediction in ER+, Node-Positive Breast Cancer. J. Pers. Med. 2023, 13, 1476. [Google Scholar] [CrossRef]
  12. Jung, H.A.; Park, Y.H.; Kim, M.; Kim, S.; Chang, W.J.; Choi, M.K.; Hong, J.Y.; Kim, S.W.; Kil, W.H.; Lee, J.E. Prognostic relevance of biological subtype overrides that of TNM staging in breast cancer: Discordance between stage and biology. Tumor Biol. 2015, 36, 1073–1079. [Google Scholar] [CrossRef] [PubMed]
  13. Luo, S.-P.; Wu, Q.-S.; Chen, H.; Wang, X.-X.; Chen, Q.-X.; Zhang, J.; Song, C.-G. Validation of the prognostic significance of the prognostic stage group according to the eighth edition of American Cancer Joint Committee on Cancer Staging System in triple-negative breast cancer: An analysis from surveillance, epidemiology, and end results 18 database. J. Surg. Res. 2020, 247, 211–219. [Google Scholar] [PubMed]
  14. American College of Surgeons. National Cancer Database. Available online: https://www.facs.org/quality-programs/cancer-programs/national-cancer-database/ (accessed on 6 December 2022).
  15. Hilsenbeck, S.G. Time-dependence of hazard ratios for prognostic factors in primary breast cancer. Breast Cancer Res. Treat. 1998, 52, 227–237. [Google Scholar] [CrossRef]
  16. Yu, K.-D.; Wu, J.; Shen, Z.-Z.; Shao, Z.-M. Hazard of breast cancer-specific mortality among women with estrogen receptor-positive breast cancer after five years from diagnosis: Implication for extended endocrine therapy. J. Clin. Endocrinol. Metab. 2012, 97, E2201–E2209. [Google Scholar] [CrossRef]
  17. Prat, A.; Pineda, E.; Adamo, B.; Galván, P.; Fernández, A.; Gaba, L.; Díez, M.; Viladot, M.; Arance, A.; Muñoz, M. Clinical implications of the intrinsic molecular subtypes of breast cancer. Breast 2015, 24, S26–S35. [Google Scholar] [CrossRef]
  18. Hammond, M.E.H.; Hayes, D.F.; Dowsett, M.; Allred, D.C.; Hagerty, K.L.; Badve, S.; Fitzgibbons, P.L.; Francis, G.; Goldstein, N.S.; Hayes, M. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch. Pathol. Lab. Med. 2010, 134, e48–e72. [Google Scholar] [CrossRef]
  19. Group, E.B.C.T.C. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: Patient-level meta-analysis of randomised trials. Lancet 2011, 378, 771–784. [Google Scholar]
  20. Eggemann, H.; Ignatov, T.; Burger, E.; Kantelhardt, E.J.; Fettke, F.; Thomssen, C.; Costa, S.D.; Ignatov, A. Moderate HER2 expression as a prognostic factor in hormone receptor positive breast cancer. Endocr. Relat. Cancer 2015, 22, 725–733. [Google Scholar] [CrossRef]
  21. Abdel-Rahman, O. Assessment of the prognostic and discriminating value of the novel bioscore system for breast cancer; a SEER database analysis. Breast Cancer Res. Treat. 2017, 164, 231–236. [Google Scholar] [CrossRef]
  22. Ross, J.S.; Slodkowska, E.A.; Symmans, W.F.; Pusztai, L.; Ravdin, P.M.; Hortobagyi, G.N. The HER-2 receptor and breast cancer: Ten years of targeted anti–HER-2 therapy and personalized medicine. Oncologist 2009, 14, 320–368. [Google Scholar] [CrossRef]
  23. Denkert, C.; Liedtke, C.; Tutt, A.; von Minckwitz, G. Molecular alterations in triple-negative breast cancer—The road to new treatment strategies. Lancet 2017, 389, 2430–2442. [Google Scholar] [CrossRef] [PubMed]
  24. Li, X.; Yang, J.; Peng, L.; Sahin, A.A.; Huo, L.; Ward, K.C.; O’Regan, R.; Torres, M.A.; Meisel, J.L. Triple-negative breast cancer has worse overall survival and cause-specific survival than non-triple-negative breast cancer. Breast Cancer Res. Treat. 2017, 161, 279–287. [Google Scholar] [CrossRef] [PubMed]
  25. Rakha, E.A.; Reis-Filho, J.S.; Baehner, F.; Dabbs, D.J.; Decker, T.; Eusebi, V.; Fox, S.B.; Ichihara, S.; Jacquemier, J.; Lakhani, S.R. Breast cancer prognostic classification in the molecular era: The role of histological grade. Breast Cancer Res. 2010, 12, 207. [Google Scholar] [CrossRef] [PubMed]
  26. Schwartz, A.M.; Henson, D.E.; Chen, D.; Rajamarthandan, S. Histologic grade remains a prognostic factor for breast cancer regardless of the number of positive lymph nodes and tumor size: A study of 161 708 cases of breast cancer from the SEER Program. Arch. Pathol. Lab. Med. 2014, 138, 1048–1052. [Google Scholar] [CrossRef]
  27. Weiss, A.; Chavez-MacGregor, M.; Lichtensztajn, D.Y.; Yi, M.; Tadros, A.; Hortobagyi, G.N.; Giordano, S.H.; Hunt, K.K.; Mittendorf, E.A. Validation study of the American Joint Committee on Cancer eighth edition prognostic stage compared with the anatomic stage in breast cancer. JAMA Oncol. 2018, 4, 203–209. [Google Scholar] [CrossRef]
  28. Ding, J.; Jiang, L.; Xu, Z.; Chen, Y.; Wu, W.; Huang, J. Validation of the Prognostic Stage from the American Joint Committee on Cancer 8th Staging Manual in Luminal B-Like Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer. Cancer Manag. Res. 2022, 14, 719–728. [Google Scholar] [CrossRef]
  29. Yang, P.; Peng, Q.-Q.; Lian, W.; Fu, F.; Wang, C.; Chen, D. Validation of the Eighth American Joint Committee on Cancer Anatomic and Prognostic Staging System for Breast Cancer. J. Surg. Res. 2022, 270, 539–546. [Google Scholar] [CrossRef]
  30. Aldrees, R.; Gao, X.; Zhang, K.; Siegal, G.P.; Wei, S. Validation of the revised 8th AJCC breast cancer clinical prognostic staging system: Analysis of 5321 cases from a single institution. Mod. Pathol. 2021, 34, 291–299. [Google Scholar] [CrossRef]
  31. Jang, N.; Choi, J.E.; Kang, S.H.; Bae, Y.K. Validation of the pathological prognostic staging system proposed in the revised eighth edition of the AJCC staging manual in different molecular subtypes of breast cancer. Virchows Arch. 2019, 474, 193–200. [Google Scholar] [CrossRef]
  32. Wang, M.; Chen, H.; Wu, K.; Ding, A.; Zhang, M.; Zhang, P. Evaluation of the prognostic stage in the 8th edition of the American Joint Committee on Cancer in locally advanced breast cancer: An analysis based on SEER 18 database. Breast 2018, 37, 56–63. [Google Scholar] [CrossRef]
  33. Ibis, K.; Ozkurt, S.; Kucucuk, S.; Yavuz, E.; Saip, P. Comparison of pathological prognostic stage and anatomic stage groups according to the updated version of the American Joint Committee on Cancer (AJCC) breast cancer staging 8th edition. Med. Sci. Monit. Int. Med. J. Exp. Clin. Res. 2018, 24, 3637. [Google Scholar] [CrossRef] [PubMed]
  34. Tokunaga, E.; Ijichi, H.; Tajiri, W.; Masuda, T.; Takizawa, K.; Ueo, H.; Koga, C.; Tanaka, J.; Nakamura, Y.; Ohno, S. The comparison of the anatomic stage and pathological prognostic stage according to the AJCC 8th edition for the prognosis in Japanese breast cancer patients: Data from a single institution. Breast Cancer 2020, 27, 1137–1146. [Google Scholar] [CrossRef] [PubMed]
  35. Pan, H.; Gray, R.; Braybrooke, J.; Davies, C.; Taylor, C.; McGale, P.; Peto, R.; Pritchard, K.I.; Bergh, J.; Dowsett, M. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N. Engl. J. Med. 2017, 377, 1836–1846. [Google Scholar] [CrossRef] [PubMed]
  36. Colleoni, M.; Sun, Z.; Price, K.N.; Karlsson, P.; Forbes, J.F.; Thürlimann, B.; Gianni, L.; Castiglione, M.; Gelber, R.D.; Coates, A.S. Annual hazard rates of recurrence for breast cancer during 24 years of follow-up: Results from the international breast cancer study group trials I to V. J. Clin. Oncol. 2016, 34, 927. [Google Scholar] [CrossRef]
  37. Park, S.; Park, B.-W.; Kim, T.H.; Jeon, C.W.; Kang, H.-S.; Choi, J.-E.; Hwang, K.-T.; Kim, I.C. Lack of either estrogen or progesterone receptor expression is associated with poor survival outcome among luminal A breast cancer subtype. Ann. Surg. Oncol. 2013, 20, 1505–1513. [Google Scholar] [CrossRef]
  38. Cartwright, L.A.; Dumenci, L.; Siminoff, L.A.; Matsuyama, R.K. Cancer patients’ understanding of prognostic information. J. Cancer Educ. 2014, 29, 311–317. [Google Scholar] [CrossRef]
  39. Guhan, M.; Crane, S.M.; Valerius, L.S.; De La Cruz, D.; Smith, B.D.; Woodward, W.A.; Mitchell, M.P.; Valero, V.; Rauch, G.M.; Krishnamurthy, S. Patient interest in exploring nonsurgical treatment approaches for early-stage breast cancer: A qualitative study. Int. J. Radiat. Oncol. Biol. Phys. 2024, 118, 443–454. [Google Scholar] [CrossRef]
  40. National Comprehensive Cancer Network, Inc. National Comprehensive Cancer Network (NCCN) Guidelines Version 1.2024-Breast Cancer 2024. Available online: https://www.nccn.org/ (accessed on 1 July 2024).
  41. Johnston, S.R.; Harbeck, N.; Hegg, R.; Toi, M.; Martin, M.; Shao, Z.M.; Zhang, Q.Y.; Rodriguez, J.L.M.; Campone, M.; Hamilton, E. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2−, node-positive, high-risk, early breast cancer (monarchE). J. Clin. Oncol. 2020, 38, 3987. [Google Scholar] [CrossRef]
  42. Slamon, D.; Lipatov, O.; Nowecki, Z.; McAndrew, N.; Kukielka-Budny, B.; Stroyakovskiy, D.; Yardley, D.A.; Huang, C.-S.; Fasching, P.A.; Crown, J. Ribociclib plus Endocrine Therapy in Early Breast Cancer. N. Engl. J. Med. 2024, 390, 1080–1091. [Google Scholar] [CrossRef]
  43. Salvo, E.M.; Ramirez, A.O.; Cueto, J.; Law, E.H.; Situ, A.; Cameron, C.; Samjoo, I.A. Risk of recurrence among patients with HR-positive, HER2-negative, early breast cancer receiving adjuvant endocrine therapy: A systematic review and meta-analysis. Breast 2021, 57, 5–17. [Google Scholar] [CrossRef]
  44. Waks, A.G.; Winer, E.P. Breast cancer treatment: A review. JAMA 2019, 321, 288–300. [Google Scholar] [CrossRef] [PubMed]
  45. Howlader, N.; Altekruse, S.F.; Li, C.I.; Chen, V.W.; Clarke, C.A.; Ries, L.A.; Cronin, K.A. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J. Natl. Cancer Inst. 2014, 106, dju055. [Google Scholar] [CrossRef] [PubMed]
  46. Soni, P.D.; Hartman, H.E.; Dess, R.T.; Abugharib, A.; Allen, S.G.; Feng, F.Y.; Zietman, A.L.; Jagsi, R.; Schipper, M.J.; Spratt, D.E. Comparison of population-based observational studies with randomized trials in oncology. J. Clin. Oncol. 2019, 37, 1209. [Google Scholar] [CrossRef] [PubMed]
Cancers 16 03830 g001aCancers 16 03830 g001b
Figure 1. Kaplan–Meier curve for survival between locally advanced HR+/HER2- breast cancer (LA- HR+/HER2- BC) and early-stage triple-negative breast cancer (ES-TNBC) among (a) the entire cohort and (b) patients receiving all appropriate standard treatment. Among the entire cohort, patients with LA-HR+/HER2- BC had 63% relative increased risk of death compared to those with ES-TNBC after adjusting for all covariates (p < 0.0001). Among patients receiving all appropriate standard treatments, patients with LA-HR+/HER2- BC had a 35% relative increased risk of death compared to those with ES-TNBC after adjusting for all covariates (p < 0.0001).
Figure 1. Kaplan–Meier curve for survival between locally advanced HR+/HER2- breast cancer (LA- HR+/HER2- BC) and early-stage triple-negative breast cancer (ES-TNBC) among (a) the entire cohort and (b) patients receiving all appropriate standard treatment. Among the entire cohort, patients with LA-HR+/HER2- BC had 63% relative increased risk of death compared to those with ES-TNBC after adjusting for all covariates (p < 0.0001). Among patients receiving all appropriate standard treatments, patients with LA-HR+/HER2- BC had a 35% relative increased risk of death compared to those with ES-TNBC after adjusting for all covariates (p < 0.0001).
Cancers 16 03830 g001aCancers 16 03830 g001b
Cancers 16 03830 g002
Figure 2. Kaplan–Meier curve for overall survival from landmark analysis (patients with ≥ 54 months of follow-up) between locally advanced HR+/HER2- breast cancer (LA- HR+/HER2- BC) and early-stage triple-negative breast cancer (ES-TNBC) among (a) the entire cohort and (b) patients receiving all appropriate standard treatment. Among the entire cohort, patients with LA-HR+/HER2- BC had 126% relative increased risk of death compared to those with ES-TNBC after adjusting for all covariates (p < 0.0001). Among patients receiving all appropriate standard treatment, patients with LA-HR+/HER2- BC had a 130% relative increased risk of death compared to those with ES-TNBC after adjusting for all covariates (p < 0.0001).
Figure 2. Kaplan–Meier curve for overall survival from landmark analysis (patients with ≥ 54 months of follow-up) between locally advanced HR+/HER2- breast cancer (LA- HR+/HER2- BC) and early-stage triple-negative breast cancer (ES-TNBC) among (a) the entire cohort and (b) patients receiving all appropriate standard treatment. Among the entire cohort, patients with LA-HR+/HER2- BC had 126% relative increased risk of death compared to those with ES-TNBC after adjusting for all covariates (p < 0.0001). Among patients receiving all appropriate standard treatment, patients with LA-HR+/HER2- BC had a 130% relative increased risk of death compared to those with ES-TNBC after adjusting for all covariates (p < 0.0001).
Cancers 16 03830 g002
Table 1. Patient characteristics.
Table 1. Patient characteristics.
Entire Cohort
(N = 45,818)		LA-HR+/HER2- BC
(N = 17,359)		ES-TNBC
(N = 28,459)
Age
          <40 years 2224 (4.8%)920 (5.3%)1304 (4.6%)
         40–49 years 7940 (17.3%)3894 (22.4%)4046 (14.2%)
         50–59 years 12,304 (26.9%)4609 (26.5%)7695 (27.0%)
         60–69 years 13,129 (28.7%)4350 (25.1%)8779 (30.9%)
         ≥70 years 10,221 (22.3%)3586 (20.7%)6635 (23.3%)
Comorbidities
         037,821 (82.6%)14,398 (82.9%)23,423 (82.3%)
         1 or more7997 (17.4%)2961 (17.1%)5036 (17.7%)
Treatment Facility
         Academic13,040 (28.4%)4736 (27.3%)8304 (29.2%)
         Other30,554 (66.7%)11,703 (67.4%)18,851 (66.2%)
         Unknown2224 (4.9%)920 (5.3%)1304 (4.6%)
Race/Ethnicity
         White33,343 (72.8%)13,186 (76.0%)20,157 (70.8%)
         Black6815 (14.9%)1709 (9.8%)5106 (17.9%)
         Hispanic ^2551 (5.6%)1181 (6.8%)1370 (4.8%)
         Asian1362 (2.9%)608 (3.5%)754 (2.7%)
         Other315 (0.7%)140 (0.8%)175 (0.6%)
         Unknown Race or Ethnicity1432 (3.1%)535 (3.1%)897 (3.2%)
Insurance Status
         Private25,306 (55.2%)9720 (56.0%)15,586 (54.8%)
         Government19,236 (42.0%)7045 (40.6%)12,191 (42.8%)
         Uninsured792 (1.7%)384 (2.2%)408 (1.4%)
         Unknown484 (1.1%)210 (1.2%)274 (1.0%)
Median Income *
         ≥USD 63,000/year14,564 (31.8%)55,89 (32.2%)8975 (31.5%)
         <USD 63,000/year25,451 (55.6%)9498 (54.7%)15,953 (56.1%)
         Unknown5803 (12.6%)2272 (13.1%)3531 (12.4%)
No High School Diploma *
         ≥13.0%16,031 (35.0%)5993 (34.5%)10,038 (35.3%)
         <13.0%23,998 (52.4%)9101 (52.4%)14,897 (52.3%)
         Unknown5789 (12.6%)2265 (13.1%)3524 (12.4%)
Anatomic Stage
         IA, G2–328,459 (62.1%)N/A28,459 (100%)
         IIIA (pT3N1), G1–24295 (9.4%)4296 (24.7%)N/A
         IIIB (pT1-3N2), G1–213,064 (28.5%)13,064 (75.3%)N/A
* Measured by matching zip code of the patient recorded at time of diagnosis against files derived from the American Community Survey data; ^—all other racial categories not listed as “Hispanic” are specifically coded as non-Hispanic; abbreviations: LA-HR+/HER2- - locally-advanced hormone receptor-positive (including estrogen- and progesterone-receptor-positive) and HER2-negative; ES-TNBC—early-stage triple-negative breast cancer; G—grade; N/A—not available.
Table 2. Summary of treatments delivered by anatomic stage group.
Table 2. Summary of treatments delivered by anatomic stage group.
Treatment TypeLA-HR+/HER2- BC
(N = 17,359)		ES-TNBC
(N = 28,459)
Breast Surgery
            Mastectomy12,834 (73.9%)7547 (26.5%)
            Lumpectomy4525 (26.1%)20,912 (73.5%)
Radiation Therapy *
            Yes13,932 (80.3%)18,501 (88.5%)
            No2774 (16.0%)1905 (9.1%)
            Unknown/Other Site653 (3.7%)506 (2.4%)
Chemotherapy
            Yes13,795 (79.5%)20,724 (72.8%)
            No3437 (19.8%)7624 (26.1%)
            Unknown127 (0.7%)311 (1.1%)
Endocrine Therapy
            Yes15,756 (90.8%)N/A
            No 1575 (9.0%)N/A
            Unknown28 (0.2%)N/A
All Appropriate Treatments **
            Yes11,533 (66.4%)19,512 (68.6%)
            No5826 (33.6%)8947 (31.4%)
* For patients with ES-TNBC, reported only for lumpectomy patients; ** For LA-HR+/HER2- BC patients, this includes receipt of radiation therapy, chemotherapy, and endocrine therapy. For patients with ES-TNBC, this includes radiation and chemotherapy for patients that had lumpectomy and chemotherapy for patients that had mastectomy; abbreviations: LA-HR+/HER2- - locally-advanced hormone receptor-positive (including estrogen- and progesterone-receptor-positive) and HER2-negative; ES-TNBC—early-stage triple-negative breast cancer; N/A—not available
Table 3. Multivariable analysis of patients receiving all recommended treatments.
Table 3. Multivariable analysis of patients receiving all recommended treatments.
HR (95% CI)p-Value
LA-HR+/HER2- BC vs. ES-TNBC1.35 (1.24–1.48)<0.0001 *
Age
          <40 years1.13 (0.90–1.42)0.298
          40–49 years0.89 (0.77–1.02)0.096
          50–59 yearsReferenceReference
          60–69 years 1.00 (0.88–1.13)0.987
          ≥70 years1.46 (1.26–1.70)<0.001 *
1+ v 0 comorbidities1.44 (1.29–1.61)<0.0001 *
Race/Ethnicity
          WhiteReferenceReference
          Black1.30 (1.15–1.47)<0.001 *
          Hispanic ^0.83 (0.66–1.04)0.102
          Asian0.63 (0.44–0.90)0.010 *
          Other0.86 (0.46–1.61)0.641
          Unknown Race/Ethnicity0.90 (0.70–1.16)0.401
Insurance Status
          Private insuranceReferenceReference
          Government insurance1.75 (1.57–1.95)<0.001 *
          No insurance1.40 (1.01–1.94)0.041 *
          Unknown insurance1.05 (0.64–1.72)0.845
Median income
          ≥USD 63 K/yearReferenceReference
          <USD 63 K/year1.17 (1.04–1.32)0.008 *
          Unknown1.60 (0.23–11.40)0.638
Facility Type
          AcademicReferenceReference
          Non-academic1.15 (1.03–1.27)0.011 *
          Unknown--
LA-HR+/HER2- BC—locally advanced hormone-receptor-positive (including estrogen- and progesterone-receptor-positive) and HER2-negative breast cancer; ES-TNBC—early-stage triple-negative breast cancer; HR—hazard ratio; CI—confidence interval; * Statistically significant with p < 0.05; ^—all other racial categories not listed as “Hispanic” are specifically coded as non-Hispanic.
Table 4. Multivariable analysis of patients receiving all recommended treatments included in the landmark analysis with ≥ 54 months of follow-up).
Table 4. Multivariable analysis of patients receiving all recommended treatments included in the landmark analysis with ≥ 54 months of follow-up).
HR (95% CI)p-Value
LA-HR+/HER2- BC vs. ES-TNBC2.30 (1.99 – 2.66)<0.0001 *
Age
          <40 years1.17 (0.82–1.66)0.395
          40–49 years0.77 (0.61–0.97)0.025 *
          50–59 yearsReferenceReference
          60–69 years 1.03 (0.84–1.25)0.788
          ≥70 years1.73 (1.36–2.21)<0.001 *
1+ v 0 comorbidities1.58 (1.33–1.88)<0.0001 *
Race/Ethnicity
          WhiteReferenceReference
          Black1.27 (1.04–1.56)<0.020 *
          Hispanic ^0.60 (0.40–0.91)0.016 *
          Asian0.57 (0.32–1.01)0.055
          Other0.46 (0.11–1.83)0.268
          Unknown Race/Ethnicity0.82 (0.56–1.20)0.316
Insurance Status
          Private insuranceReferenceReference
          Government insurance1.54 (1.29–1.84)<0.0001 *
          No insurance1.64 (1.03–2.62)0.036 *
          Unknown insurance1.13 (0.56–2.29)0.726
Median income
          ≥USD 63 K/yearReferenceReference
          <USD 63 K/year1.12 (0.92–1.34)0.255
          Unknown00 (0.00–0.00)0.959
Facility Type
          AcademicReferenceReference
          Non-academic1.10 (0.93–1.29)0.290
          Unknown--
LA-HR+/HER2- BC—Locally advanced hormone-receptor-positive (including estrogen- and progesterone-receptor-positive) and HER2-negative breast cancer; ES-TNBC—early-stage triple-negative breast cancer; HR—hazard ratio; CI—confidence interval; * Statistically significant with p < 0.05; ^—all racial categories not listed as “Hispanic” are specifically coded as non-Hispanic.
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Yoon, S.M.; Wu, S.; Schwer, A.; Glaser, S.; DeWees, T.; Bazan, J.G. Are All Prognostic Stage IB Breast Cancers Equivalent? Cancers 2024, 16, 3830. https://doi.org/10.3390/cancers16223830

AMA Style

Yoon SM, Wu S, Schwer A, Glaser S, DeWees T, Bazan JG. Are All Prognostic Stage IB Breast Cancers Equivalent? Cancers. 2024; 16(22):3830. https://doi.org/10.3390/cancers16223830

Chicago/Turabian Style

Yoon, Stephanie M., Shengyang Wu, Amanda Schwer, Scott Glaser, Todd DeWees, and Jose G. Bazan. 2024. "Are All Prognostic Stage IB Breast Cancers Equivalent?" Cancers 16, no. 22: 3830. https://doi.org/10.3390/cancers16223830

APA Style

Yoon, S. M., Wu, S., Schwer, A., Glaser, S., DeWees, T., & Bazan, J. G. (2024). Are All Prognostic Stage IB Breast Cancers Equivalent? Cancers, 16(22), 3830. https://doi.org/10.3390/cancers16223830

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