Risk of mortality of node-negative, ER/PR/HER2 breast cancer subtypes in T1, T2, and T3 tumors
- 373 Downloads
The purpose of this study was to assess differences in breast cancer-specific mortality within tumors of the same size when breast cancer was defined using the three tumor markers estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2).
We identified 104,499 cases of node-negative primary female invasive breast cancer from the California Cancer Registry. Tumor size was categorized as T1a, T1b, T1c, T2, and T3. Breast cancer was defined using ER, PR, and HER2. Kaplan–Meier Survival analysis was conducted and Cox Regression was used to compute the adjusted risk of mortality for the ER+/PR+/HER2+, ER−/PR−/HER2− (TNBC), and ER−/PR−/HER2+ (HER2-overexpressing) subtypes when compared with the ER+/PR+/HER2−. Separate models were computed for each tumor size.
Unadjusted survival analysis showed that for all tumor sizes, the ER+/PR+ subtypes regardless of HER status have better breast cancer-specific survival than ER−/PR− subtypes. Subtype was not an important factor for risk of mortality for T1a tumors. The ER+/PR+/HER2+ subtype was only a risk for mortality in T1b tumors that were unadjusted for treatment. For all other tumor sizes, the ER+/PR+/HER2+ had the same mortality as the ER+/PR+/HER2− subtype regardless of adjustment for treatment. The HER2-overexpressing subtype had a higher risk of mortality than the ER+/PR+/HER2− subtype except for T1b tumors that were adjusted for treatment. For all tumor sizes, the TNBC had higher hazard ratios than all other subtypes.
T1a tumors have the same risk of mortality regardless of ER/PR/HER2 subtype, and ER and PR negativity plays a stronger role in survival than HER2 positivity for tumors of all size.
KeywordsBreast cancer ER/PR/HER2 subtype Tumor size
We wish to thank Melissa Taylor and the staff at the Sutter Resource Library for their valuable assistance.
The collection of cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute’s Surveillance, Epidemiology and End Results Program under contract N01-PC-35136 awarded to the Northern California Cancer Center, contract N01-PC-35139 awarded to the University of Southern California, and contract N01-PC-54404 awarded to the Public Health Institute; and the Centers for Disease Control and Prevention’s National Program of Cancer Registries, under agreement 1U58DP00807-01 awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the authors and endorsement by the State of California, Department of Public Health the National Cancer Institute, and the Centers for Disease Control and Prevention or their Contractors and Subcontractors is not intended nor should be inferred.
This study was funded by Grant 947110-1107555 from the Sutter Medical Center Sacramento Foundation.
Compliance and ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This research study involved analysis of existing data from the CCR without subject identifiers or intervention. Therefore, the study was categorized as exempt from institutional review board oversight.
- 3.Mandelblatt JS, Stout NK, Schechter CB, van den Broek JJ, Miglioretti DL, Krapcho M, Trentham-Dietz A, Munoz D, Lee SJ, Berry DA, van Ravesteyn NT, Alagoz O, Kerlikowske K, Tosteson AN, Near AM, Hoeffken A, Chang Y, Heijnsdijk EA, Chisholm G, Huang X, Huang H, Ergun MA, Gangnon R, Sprague BL, Plevritis S, Feuer E, de Koning HJ, Cronin KA (2016) Collaborative modeling of the benefits and harms associated with different U.S. breast cancer screening strategies. Ann Intern Med 164(4):215–225. doi: 10.7326/M15-1536 CrossRefPubMedPubMedCentralGoogle Scholar
- 4.Curigliano G, Viale G, Bagnardi V, Fumagalli L, Locatelli M, Rotmensz N, Ghisini R, Colleoni M, Munzone E, Veronesi P, Zurrida S, Nole F, Goldhirsch A (2009) Clinical relevance of HER2 overexpression/amplification in patients with small tumor size and node-negative breast cancer. J Clin Oncol 27(34):5693–5699. doi: 10.1200/JCO.2009.22.0962 CrossRefPubMedGoogle Scholar
- 5.Gonzalez-Angulo AM, Litton JK, Broglio KR, Meric-Bernstam F, Rakkhit R, Cardoso F, Peintinger F, Hanrahan EO, Sahin A, Guray M, Larsimont D, Feoli F, Stranzl H, Buchholz TA, Valero V, Theriault R, Piccart-Gebhart M, Ravdin PM, Berry DA, Hortobagyi GN (2009) High risk of recurrence for patients with breast cancer who have human epidermal growth factor receptor 2-positive, node-negative tumors 1 cm or smaller. J Clin Oncol 27(34):5700–5706. doi: 10.1200/JCO.2009.23.2025 CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Cancello G, Maisonneuve P, Rotmensz N, Viale G, Mastropasqua MG, Pruneri G, Montagna E, Dellapasqua S, Iorfida M, Cardillo A, Veronesi P, Luini A, Intra M, Gentilini O, Scarano E, Goldhirsch A, Colleoni M (2011) Prognosis in women with small (T1mic, T1a, T1b) node-negative operable breast cancer by immunohistochemically selected subtypes. Breast Cancer Res Treat 127(3):713–720. doi: 10.1007/s10549-011-1465-7 CrossRefPubMedGoogle Scholar
- 7.Vaz-Luis I, Ottesen RA, Hughes ME, Mamet R, Burstein HJ, Edge SB, Gonzalez-Angulo AM, Moy B, Rugo HS, Theriault RL, Weeks JC, Winer EP, Lin NU (2014) Outcomes by tumor subtype and treatment pattern in women with small, node-negative breast cancer: a multi-institutional study. J Clin Oncol 32(20):2142–2150. doi: 10.1200/JCO.2013.53.1608 CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Parise CA, Bauer KR, Brown MM, Caggiano V (2009) Breast cancer subtypes as defined by the estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2) among women with invasive breast cancer in California, 1999–2004. Breast Journal 15(6):593–602. doi: 10.1111/j.1524-4741.2009.00822.x CrossRefPubMedGoogle Scholar
- 11.Fritz AG (2000) International classification of diseases for oncology: ICD-O, 3rd edn. World Health Organization, GenevaGoogle Scholar
- 12.Cancer reporting in California: abstracting and coding procedures for hospitals. California cancer reporting system standards, vol. I (2008). California Department of Public, Cancer Surveillance and Research Branch, SacramentoGoogle Scholar
- 13.ICD10Data.com. http://www.icd10data.com/. Accessed Jan 2016
- 14.DAKO (2003) HERCEPTest® Information Web site. Summary of Procedure. http://www.herceptin.com/herceptin/professional/testing/faqs.jsp. Accessed June 2006
- 15.PathVysion® (2002) HER-2 DNA Probe Kit Package Insert, vol. February. Vysis, Inc.Google Scholar
- 16.American Community Survey (2016) U.S. Department of Commerce, United States Census Bureau https://www.census.gov/programs-surveys/acs/. Accessed Jan 2016
- 20.Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V (2007) Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California Cancer Registry. Cancer 109(9):1721–1728CrossRefGoogle Scholar
- 27.(2012) IBM SPSS Statistics for Windows, vol. 21.0. IBM Corp, ArmonkGoogle Scholar
- 28.Subramaniam S, Bhoo-Pathy N, Taib NA, Tan GH, See MH, Jamaris S, Ho GF, Looi LM, Yip CH (2015) Breast cancer outcomes as defined by the estrogen receptor, progesterone receptor, and human growth factor receptor-2 in a multi-ethnic Asian country. World J Surg 39(10):2450–2458. doi: 10.1007/s00268-015-3133-2 CrossRefPubMedGoogle Scholar