Journal Article
. 2020 Jul;9(17).
doi: 10.1002/cam4.3305.

Association of sonographic features and molecular subtypes in predicting breast cancer disease outcomes

Haoyu Wang 1 Jiejie Yao 2 Ying Zhu 2 Weiwei Zhan 2 Xiaosong Chen 1 Kunwei Shen 1 
  • PMID: 32657039
  •     42 References
  •     1 citations


Background: Features in preoperative ultrasound could predict the prognosis of triple-negative breast cancer (TNBC), while its prognostic value in other molecular subtypes of breast cancer (BC) was unknown. The study aimed to assess the prognostic value of preoperative sonographic features, including orientations, on long-term outcomes in BC and its association with different molecular subtypes.

Methods: Women diagnosed with invasive BC > 5 mm who underwent surgery were retrospectively reviewed. Clinical, pathological, and sonographic profiles were collected and recurrence-free survival (RFS) and breast cancer-specific survival (BCSS) were reported. Interactions between clinicopathological features and tumor orientations in predicting RFS and BCSS were analyzed. Competing risk model was performed to estimate prognostic values of sonographic features for RFS and BCSS.

Results: A total of 2812 patients were included. With a median follow-up of 60.0 months, 268 (9.5%) patients suffered from recurrences and 104 (3.7%) died of BC. The prognostic values of vertical orientation in predicting RFS (P = .001) and BCSS (P = .001) were strongly associated with molecular subtypes. Non-TNBC tumors with vertical orientation had less recurrence events compared with parallel orientation (6.3% vs 8.7%, P = .035), whereas failed to predict disease outcomes in multivariate analysis (P > .05). Oppositely, in TNBC, vertical orientation was associated with worse RFS (HR = 3.50; 95% confidence interval [CI] 1.69-7.24; P < .001) and BCSS (HR = 6.36; 95% CI 2.86-14.14; P < .001) in multivariate analysis with a 5-year RFS and BCSS of 73.4% and 74.6%. Meanwhile, vertical orientation was related with smaller tumor size (P < .001), human epidermal growth factor receptor 2 nonamplification (P < .001), and lower Ki-67 expression (P = .001) among non-TNBC population, whereas TNBC tumors with vertical orientation had a higher burden of axillary lymph node metastases (2.8 ± 1.0 vs 1.4 ± 0.2, P = .001).

Conclusions: Prognostic values of sonographic orientation in predicting BC disease outcomes were associated with molecular subtypes. Vertical orientation in preoperative sonogram may serve as a prognostic biomarker for TNBC patients.

Keywords: breast cancer; molecular subtype; prognosis; ultrasonography; vertical orientation.

Impact of Molecular Subtype Conversion of Breast Cancers after Neoadjuvant Chemotherapy on Clinical Outcome.
Siew Kuan Lim, Moo Hyun Lee, +8 authors, Eun Sook Lee.
Cancer Res Treat, 2015 Apr 14; 48(1). PMID: 25865655    Free PMC article.
Combined use of clinical and pathologic staging variables to define outcomes for breast cancer patients treated with neoadjuvant therapy.
Jacqueline S Jeruss, Elizabeth A Mittendorf, +7 authors, Kelly K Hunt.
J Clin Oncol, 2007 Dec 07; 26(2). PMID: 18056680
Triple-negative breast cancer: correlation between MR imaging and pathologic findings.
Takayoshi Uematsu, Masako Kasami, Sachiko Yuen.
Radiology, 2009 Feb 27; 250(3). PMID: 19244039
Mammography, US, and MRI to Assess Outcomes of Invasive Breast Cancer with Extensive Intraductal Component: A Matched Cohort Study.
Su Min Ha, Joo Hee Cha, +3 authors, Hak Hee Kim.
Radiology, 2019 May 29; 292(2). PMID: 31135297
Association of sonographic features and molecular subtypes in predicting breast cancer disease outcomes.
Haoyu Wang, Jiejie Yao, +3 authors, Kunwei Shen.
Cancer Med, 2020 Jul 14; 9(17). PMID: 32657039    Free PMC article.
Breast Cancer Screening and Diagnosis, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology.
Therese B Bevers, Mark Helvie, +28 authors, Rashmi Kumar.
J Natl Compr Canc Netw, 2018 Nov 18; 16(11). PMID: 30442736
Highly Cited.
Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer.
Joseph A Sparano, Robert J Gray, +27 authors, George W Sledge.
N Engl J Med, 2019 Jun 04; 380(25). PMID: 31157962    Free PMC article.
Highly Cited.
Assessing Risk Category of Breast Cancer by Ultrasound Imaging Characteristics.
Qiang Guo, Lei Zhang, +7 authors, Jiawei Tian.
Ultrasound Med Biol, 2018 Jan 15; 44(4). PMID: 29331358
Clinical relevance of host immunity in breast cancer: from TILs to the clinic.
Peter Savas, Roberto Salgado, +4 authors, Sherene Loi.
Nat Rev Clin Oncol, 2015 Dec 17; 13(4). PMID: 26667975
Highly Cited. Review.
Rapid review: radiomics and breast cancer.
Francesca Valdora, Nehmat Houssami, +2 authors, Alberto Stefano Tagliafico.
Breast Cancer Res Treat, 2018 Feb 06; 169(2). PMID: 29396665
Highly Cited. Review.
Role of color Doppler indices in predicting disease-free survival of breast cancer patients during neoadjuvant chemotherapy.
Gurpreet Singh, Pratik Kumar, +3 authors, Norbert Hosten.
Eur J Radiol, 2010 Jan 15; 75(2). PMID: 20071116
Correlation of sonographic features of invasive ductal mammary carcinoma with age, tumor grade, and hormone-receptor status.
Michael Aho, Abid Irshad, +7 authors, Joan E Cunningham.
J Clin Ultrasound, 2012 Sep 22; 41(1). PMID: 22996916    Free PMC article.
Subtype-Dependent Relationship Between Young Age at Diagnosis and Breast Cancer Survival.
Ann H Partridge, Melissa E Hughes, +9 authors, Rulla M Tamimi.
J Clin Oncol, 2016 Aug 03; 34(27). PMID: 27480155
Highly Cited.
Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update.
Antonio C Wolff, M Elizabeth Hale Hammond, +14 authors, Mitchell Dowsett.
Arch Pathol Lab Med, 2018 May 31; 142(11). PMID: 29846104
Highly Cited.
Color Doppler ultrasonography for treatment response prediction and evaluation in breast cancer.
Anand Kumar, Vivek Srivastava, Seema Singh, Ram Chandra Shukla.
Future Oncol, 2010 Aug 31; 6(8). PMID: 20799873
Absolute Benefit of Adjuvant Endocrine Therapies for Premenopausal Women With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer: TEXT and SOFT Trials.
Meredith M Regan, Prudence A Francis, +12 authors, Richard D Gelber.
J Clin Oncol, 2016 Apr 06; 34(19). PMID: 27044936    Free PMC article.
Association between Ultrasound Features and the 21-Gene Recurrence Score Assays in Patients with Oestrogen Receptor-Positive, HER2-Negative, Invasive Breast Cancer.
Eun Young Chae, Woo Kyung Moon, +8 authors, Sei Hyun Ahn.
PLoS One, 2016 Jul 01; 11(6). PMID: 27362843    Free PMC article.
Supplemental Screening for Breast Cancer in Women With Dense Breasts: A Systematic Review for the U.S. Preventive Services Task Force.
Joy Melnikow, Joshua J Fenton, +4 authors, Kunal Shah.
Ann Intern Med, 2016 Jan 13; 164(4). PMID: 26757021    Free PMC article.
Highly Cited. Systematic Review.
Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013.
A Goldhirsch, E P Winer, +5 authors, Panel members.
Ann Oncol, 2013 Aug 07; 24(9). PMID: 23917950    Free PMC article.
Highly Cited.
Triple-negative breast cancers: associations between imaging and pathological findings for triple-negative tumors compared with hormone receptor-positive/human epidermal growth factor receptor-2-negative breast cancers.
Martine Boisserie-Lacroix, Gaëtan Macgrogan, +6 authors, Gabrielle Hurtevent-Labrot.
Oncologist, 2013 Jul 04; 18(7). PMID: 23821326    Free PMC article.
Sonography with vertical orientation feature predicts worse disease outcome in triple negative breast cancer.
Haoyu Wang, Weiwei Zhan, +3 authors, Kunwei Shen.
Breast, 2019 Nov 05; 49. PMID: 31677531    Free PMC article.
Breast cancer detection using sonography in women with mammographically dense breasts.
Jimmy Okello, Harriet Kisembo, Sam Bugeza, Moses Galukande.
BMC Med Imaging, 2014 Dec 31; 14. PMID: 25547239    Free PMC article.
Cancer statistics, 2020.
Rebecca L Siegel, Kimberly D Miller, Ahmedin Jemal.
CA Cancer J Clin, 2020 Jan 09; 70(1). PMID: 31912902
Highly Cited.
Ki67 Changes Identify Worse Outcomes in Residual Breast Cancer Tumors After Neoadjuvant Chemotherapy.
Paula Cabrera-Galeana, Wendy Muñoz-Montaño, +9 authors, Oscar Arrieta.
Oncologist, 2018 Mar 02; 23(6). PMID: 29490940    Free PMC article.
Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial.
Peter Schmid, Hope S Rugo, +13 authors, IMpassion130 Investigators.
Lancet Oncol, 2019 Dec 02; 21(1). PMID: 31786121
Highly Cited.
American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version).
M Elizabeth H Hammond, Daniel F Hayes, +31 authors, College of American Pathologists.
Arch Pathol Lab Med, 2010 Jul 01; 134(7). PMID: 20586616
Highly Cited. Systematic Review.
Assessment of intratumoral vascularization (angiogenesis) in breast cancer prognosis.
R Heimann, D Ferguson, S Gray, S Hellman.
Breast Cancer Res Treat, 1999 Mar 05; 52(1-3). PMID: 10066079
Correlation of ultrasound findings with histology, tumor grade, and biological markers in breast cancer.
Sung Hyun Kim, Bo Kyoung Seo, +7 authors, Ju-Han Lee.
Acta Oncol, 2008 Jul 09; 47(8). PMID: 18607848
Deciphering Genomic Underpinnings of Quantitative MRI-based Radiomic Phenotypes of Invasive Breast Carcinoma.
Yitan Zhu, Hui Li, +4 authors, Yuan Ji.
Sci Rep, 2015 Dec 08; 5. PMID: 26639025    Free PMC article.
Association between sonographic appearances of breast cancers and their histopathologic features and biomarkers.
Melania Costantini, Paolo Belli, +3 authors, Grazia Tomasa Bitti.
J Clin Ultrasound, 2015 Sep 25; 44(1). PMID: 26402438
BI-RADS update.
Cecilia L Mercado.
Radiol Clin North Am, 2014 May 06; 52(3). PMID: 24792650
Loss of HER2 positivity and prognosis after neoadjuvant therapy in HER2-positive breast cancer patients.
V Guarneri, M V Dieci, +5 authors, P F Conte.
Ann Oncol, 2013 Sep 10; 24(12). PMID: 24013581
Strategies for subtypes--dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011.
A Goldhirsch, W C Wood, +4 authors, Panel members.
Ann Oncol, 2011 Jun 29; 22(8). PMID: 21709140    Free PMC article.
Highly Cited.
Prognostic factors and treatment decisions in axillary-node-negative breast cancer.
W L McGuire, G M Clark.
N Engl J Med, 1992 Jun 25; 326(26). PMID: 1594018
Sonographic features of triple-negative and non-triple-negative breast cancer.
Sebastian Wojcinski, Amr A Soliman, +3 authors, Peter Hillemanns.
J Ultrasound Med, 2012 Sep 27; 31(10). PMID: 23011616
Sonobreast: predicting individualized probabilities of malignancy in solid breast masses with echographic expression.
Régis Resende Paulinelli, Ruffo Freitas-Junior, +8 authors, Danilo Augusto Teixeira.
Breast J, 2011 Feb 11; 17(2). PMID: 21306470
Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009.
A Goldhirsch, J N Ingle, +4 authors, Panel members.
Ann Oncol, 2009 Jun 19; 20(8). PMID: 19535820    Free PMC article.
Highly Cited.
Pre-operative stromal stiffness measured by shear wave elastography is independently associated with breast cancer-specific survival.
Andy Evans, Yee Ting Sim, +7 authors, Paul Pharoah.
Breast Cancer Res Treat, 2018 Jun 03; 171(2). PMID: 29858751    Free PMC article.
A priori Prediction of Neoadjuvant Chemotherapy Response and Survival in Breast Cancer Patients using Quantitative Ultrasound.
Hadi Tadayyon, Lakshmanan Sannachi, +8 authors, Gregory J Czarnota.
Sci Rep, 2017 Apr 13; 7. PMID: 28401902    Free PMC article.
Global burden of breast cancer and attributable risk factors in 195 countries and territories, from 1990 to 2017: results from the Global Burden of Disease Study 2017.
Na Li, Yujiao Deng, +10 authors, Zhijun Dai.
J Hematol Oncol, 2019 Dec 23; 12(1). PMID: 31864424    Free PMC article.
Breast Cancer Detected at Screening US: Survival Rates and Clinical-Pathologic and Imaging Factors Associated with Recurrence.
Soo-Yeon Kim, Boo-Kyung Han, +4 authors, Woo Kyung Moon.
Radiology, 2017 Apr 08; 284(2). PMID: 28387638
Triple-negative invasive breast carcinoma: the association between the sonographic appearances with clinicopathological feature.
Jia-Wei Li, Kai Zhang, +4 authors, Cai Chang.
Sci Rep, 2018 Jun 15; 8(1). PMID: 29899425    Free PMC article.
Association of sonographic features and molecular subtypes in predicting breast cancer disease outcomes.
Haoyu Wang, Jiejie Yao, +3 authors, Kunwei Shen.
Cancer Med, 2020 Jul 14; 9(17). PMID: 32657039    Free PMC article.