Estrogen Receptor, Progesterone Receptor, and HER2 Status Predict Lymphovascular Invasion and Lymph Node Involvement

Overview

Journal Ann Surg Oncol

Publisher Springer

Specialty Oncology

Date 2014 Jun 22

PMID 24952028

Citations 34

Authors

Stacy Ugras

Michelle Stempel

Sujata Patil

Monica Morrow

Affiliations

Soon will be listed here.

Abstract

Background: The ACOSOG Z0011 trial demonstrated that axillary dissection (ALND) is not necessary for local control or survival in women with T1/2cN0 cancer undergoing breast-conserving therapy. There is concern about applying these results to triple-negative (TN) cancers secondary to their high local-recurrence (LR) rate. We examined the frequency of lymphovascular invasion (LVI) and nodal metastases in TN cancers to determine whether ALND can be safely avoided in this subtype.

Methods: Data were obtained from a database of patients with invasive breast cancer treated at Memorial Sloan Kettering Cancer Center from January 1998 to December 2010. A total of 11,596 tumors were classifiable into clinical surrogates for molecular subtype by immunohistochemical analysis: hormone receptor (HR)+/HER2+, HR+/HER2-, HR-/HER2+, and TN (HR-/HER2-). Multivariable logistic regression analysis (MVA) was used to determine associations between clinicopathologic variables and subtype.

Results: There were differences in age, tumor size, LVI, grade, and nodal involvement among groups. On MVA controlling for size, grade, and age, ER, PR, and HER2 status were significantly associated with LVI (p < 0.0001). Relative to TN tumors, HR+/HER2-, HR+/HER2+, and HR-/HER2+ tumors had higher odds of demonstrating LVI of 1.8 (odds ratio 1.8; 95 % confidence interval 1.6-2.1), 2.5 (2.5; 2.0-3.0), and 1.7 (1.7; 1.4-2.1), respectively. On MVA adjusting for size, grade, LVI, and age, TN tumors had the lowest odds of having any or high-volume nodal involvement (≥4 nodes, p < 0.0001).

Conclusions: LVI and nodal metastases were least frequent in TN cancers compared with other subtypes, despite the uniformly worse prognosis and increased LR rate in TN tumors. This suggests TN cancers spread via lymphatics less frequently than other subtypes and ALND may be avoided in TN patients meeting Z0011 eligibility criteria.

Citing Articles

Factors Associated with Nodal Positivity Following Neoadjuvant Systemic Therapy in Breast Cancer Patients Who are Initially Node-Negative on MRI.

Ozcan B, Arjmandi F, Polat D, Xi Y, Sahoo S, Leitch M Ann Surg Oncol. 2025; .

PMID: 39948311 DOI: 10.1245/s10434-025-16985-8.

Nomograms for metastasis of non-sentinel lymph nodes or more than three lymph nodes in patients with one or two positive sentinel lymph nodes.

Wang X, Bi Z, Zhang J, Wang Y Front Oncol. 2024; 14:1413936.

PMID: 38835388 PMC: 11148251. DOI: 10.3389/fonc.2024.1413936.

Axillary nodal disease burden is not associated with an elevated 21-gene recurrence score in post-menopausal women presenting with a clinically negative axilla.

van den Bruele A, Paul M, Thomas S, Sammons S, DiNome M, Plichta J Am J Surg. 2024; 233:45-51.

PMID: 38350748 PMC: 11164627. DOI: 10.1016/j.amjsurg.2024.02.005.

Do HER2-Low Tumors Have a Distinct Clinicopathologic Phenotype?.

Polidorio N, Montagna G, Sevilimedu V, Le T, Morrow M Ann Surg Oncol. 2023; 31(4):2231-2243.

PMID: 38158494 PMC: 11177575. DOI: 10.1245/s10434-023-14800-w.

Ultrasound radiomics-based nomogram to predict lymphovascular invasion in invasive breast cancer: a multicenter, retrospective study.

Du Y, Cai M, Zha H, Chen B, Gu J, Zhang M Eur Radiol. 2023; 34(1):136-148.

PMID: 37518678 DOI: 10.1007/s00330-023-09995-1.

References

Viale G, Zurrida S, Maiorano E, Mazzarol G, Pruneri G, Paganelli G . Predicting the status of axillary sentinel lymph nodes in 4351 patients with invasive breast carcinoma treated in a single institution. Cancer. 2004; 103(3):492-500. DOI: 10.1002/cncr.20809. View

Metzger-Filho O, Sun Z, Viale G, Price K, Crivellari D, Snyder R . Patterns of Recurrence and outcome according to breast cancer subtypes in lymph node-negative disease: results from international breast cancer study group trials VIII and IX. J Clin Oncol. 2013; 31(25):3083-90. PMC: 3753700. DOI: 10.1200/JCO.2012.46.1574. View

Kraeima J, Siesling S, Vliegen I, Klaase J, IJzerman M . Individual risk profiling for breast cancer recurrence: towards tailored follow-up schemes. Br J Cancer. 2013; 109(4):866-71. PMC: 3749573. DOI: 10.1038/bjc.2013.401. View

Perou C, Sorlie T, Eisen M, van de Rijn M, Jeffrey S, Rees C . Molecular portraits of human breast tumours. Nature. 2000; 406(6797):747-52. DOI: 10.1038/35021093. View

Barth A, CRAIG P, Silverstein M . Predictors of axillary lymph node metastases in patients with T1 breast carcinoma. Cancer. 1997; 79(10):1918-22. View

Greer L, Rosman M, Mylander W, Liang W, Buras R, Chagpar A . A prediction model for the presence of axillary lymph node involvement in women with invasive breast cancer: a focus on older women. Breast J. 2014; 20(2):147-53. DOI: 10.1111/tbj.12233. View

Dent R, Trudeau M, Pritchard K, Hanna W, Kahn H, Sawka C . Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007; 13(15 Pt 1):4429-34. DOI: 10.1158/1078-0432.CCR-06-3045. View

Giuliano A, McCall L, Beitsch P, Whitworth P, Blumencranz P, Leitch A . Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group Z0011 randomized trial. Ann Surg. 2010; 252(3):426-32. PMC: 5593421. DOI: 10.1097/SLA.0b013e3181f08f32. View

Lanning R, Morrow M, Riaz N, McArthur H, Dang C, Moo T . The Effect of Adjuvant Trastuzumab on Locoregional Recurrence of Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Treated with Mastectomy. Ann Surg Oncol. 2015; 22(8):2517-25. DOI: 10.1245/s10434-014-4321-2. View

10.

Harvey J, Clark G, Osborne C, Allred D . Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol. 1999; 17(5):1474-81. DOI: 10.1200/JCO.1999.17.5.1474. View

11.

Kiess A, McArthur H, Mahoney K, Patil S, Morris P, Ho A . Adjuvant trastuzumab reduces locoregional recurrence in women who receive breast-conservation therapy for lymph node-negative, human epidermal growth factor receptor 2-positive breast cancer. Cancer. 2011; 118(8):1982-8. DOI: 10.1002/cncr.26484. View

12.

Kyndi M, Sorensen F, Knudsen H, Overgaard M, Nielsen H, Overgaard J . Estrogen receptor, progesterone receptor, HER-2, and response to postmastectomy radiotherapy in high-risk breast cancer: the Danish Breast Cancer Cooperative Group. J Clin Oncol. 2008; 26(9):1419-26. DOI: 10.1200/JCO.2007.14.5565. View

13.

Taylor C, Levenson R . Quantification of immunohistochemistry--issues concerning methods, utility and semiquantitative assessment II. Histopathology. 2006; 49(4):411-24. DOI: 10.1111/j.1365-2559.2006.02513.x. View

14.

Wiechmann L, Sampson M, Stempel M, Jacks L, Patil S, King T . Presenting features of breast cancer differ by molecular subtype. Ann Surg Oncol. 2009; 16(10):2705-10. DOI: 10.1245/s10434-009-0606-2. View

15.

Sorlie T, Tibshirani R, Parker J, Hastie T, Marron J, Nobel A . Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A. 2003; 100(14):8418-23. PMC: 166244. DOI: 10.1073/pnas.0932692100. View

16.

Giuliano A, Hunt K, Ballman K, Beitsch P, Whitworth P, Blumencranz P . Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011; 305(6):569-75. PMC: 5389857. DOI: 10.1001/jama.2011.90. View

17.

Yates L, Kirby A, Crichton S, Gillett C, Cane P, Fentiman I . Risk factors for regional nodal relapse in breast cancer patients with one to three positive axillary nodes. Int J Radiat Oncol Biol Phys. 2011; 82(5):2093-103. DOI: 10.1016/j.ijrobp.2011.01.066. View

18.

Adkins F, Gonzalez-Angulo A, Lei X, Hernandez-Aya L, Mittendorf E, Litton J . Triple-negative breast cancer is not a contraindication for breast conservation. Ann Surg Oncol. 2011; 18(11):3164-73. PMC: 4337779. DOI: 10.1245/s10434-011-1920-z. View

19.

Giuliano A, Hawes D, Ballman K, Whitworth P, Blumencranz P, Reintgen D . Association of occult metastases in sentinel lymph nodes and bone marrow with survival among women with early-stage invasive breast cancer. JAMA. 2011; 306(4):385-93. PMC: 5389856. DOI: 10.1001/jama.2011.1034. View

20.

Olivotto I, Jackson J, Mates D, Andersen S, Davidson W, Bryce C . Prediction of axillary lymph node involvement of women with invasive breast carcinoma: a multivariate analysis. Cancer. 1998; 83(5):948-55. View