Research

Pathologists and clinicians at the Johns Hopkins Hospital are engaged in numerous research endeavors to better understand breast cancer with the goal of ultimately curing this disease. Research on breast cancer at The Johns Hopkins Hospital can be divided into clinical and experimental research. The goal of clinical research is to optimize treatment for patients with breast cancer using various combinations of surgery, chemotherapy, immunotherapy, hormonal therapy or radiation. The goal of experimental research is to learn more about the pathogenic mechanisms such as gene changes that cause primary breast cancer and that lead to metastases. By understanding what is abnormal about the cancer cells, we will be able to find more effective and safer ways of treating patients in the future. Also, we hope to use the knowledge about the genetic abnormalities in breast cancers to better predict which patients will develop metastases and might need different up-front therapies.

Selected Breast Cancer Publications from our Group, 2008-2015

  1. Cimino-Mathews A, Thompson E, Taube JM, Ye X, Lu Y, Meeker A, Xu H, Sharma R, Lecksell K, Cornish TC, Cuka N, Argani P, Emens LA. PD-L1 (B7-H1) Expression and the Immune Tumor Microenvironment in Human Primary and Metastatic Breast Carcinomas. Hum Pathol. 2015. In press.
  2. Cimino-Mathews A, Verma S, Figueroa-Magalhaes MC, Jeter SC, Zhang Z, Argani P, Stearns V, Connolly RM. A clinicopathologic analysis of 45 patients with metaplastic breast carcinoma. Amer J Clin Pathol. In press.
  3. Heaphy CM, Asch-Kendrick R, Argani P, Meeker AK, Cimino-Mathews A. Telomere Length Alterations Unique to Invasive Lobular Carcinoma. Hum Pathol. 2015 Aug;46(8):1197-203.
  4. Cimino-Mathews A, Foote JB, Emens LA. Immune targeting in breast cancer. Oncology (Williston Park). 2015 May;29(5):375-85.
  5. Vandenbussche C, Cimino-Mathews A, Park BH, Emens LA, Tsangaris TN, Argani P. Reflex estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 (ER/PR/Her2) analysis of breast cancers in needle core biopsy specimens dramatically increases health care costs. Am J Surg Pathol. 2015 Jul;39(7):939-47.
  6. Mohseni M, Cicado J, Croessmann S, Cimino-Mathews A, Wong HY, Scharpf R, Zabransky DJ, Abukhdeir A, Garay JP, Wang GM, Beaver JA, Cochran R, Blair BG, Rosen DM, Argani P, Hurley PJ, Lauring J, Park BH. MACROD2 overexpression mediates estrogen independent growth and tamoxifen resistance in breast cancers. Proc Natl Acad Sci U S A. 2014 Dec 9;111(49):17606-11.
  7. Asch-Kendrick RJ, Samols MA, Lilo MT, Subhawong A, Sharma R, Illei PB, Argani P, Cimino-Mathews A. NKX3.1 is expressed in ER and AR positive primary breast carcinomas. J Clin Pathol. 2014 Sep;67(9):768-71.
  8. Cimino-Mathews A, Sharma R, Illei PB, Vang R, Argani P. A Subset of Malignant Phyllodes Tumors Express p63 and p40: A Diagnostic Pitfall in Breast Core Needle Biopsies. Amer J Surg Pathol. 2014 Dec;38(12):1689-96.
  9. Carney E, Cimino-Mathews A, Argani C, Kronz J, Vang R, Argani P. A subset of nondescript axillary lymph node inclusions represent endosalpingiosis. Am J Surg Pathol. 2014 Dec;38(12):1612-7.
  10. Han L, Diehl A, Nguyen NK, Korangath P, Teo W, Cho S, Kominsky S, Huso DL, Feigenbaum L, Rein A, Argani P, Landberg G, Gessler M, Sukumar S. The Notch pathway inhibits TGFβ signaling in breast cancer through HEYL-mediated crosstalk. Cancer Res. 2014 Nov 15;74(22):6509-18.
  11. Poling JS, Tsangaris TN, Argani P, Cimino-Mathews A.Frozen section evaluation of breast carcinoma sentinel lymph nodes: a retrospective review of 1,940 cases. Breast Cancer Res Treat. 2014 Nov;148(2):355-61.
  12. Beaver JA, Jelovac D, Balukrishna S, Cochran R, Croessmann S, Zabransky DJ, Wong HY, Toro PT, Cidado J, Blair BG, Chu D, Burns T, Higgins MJ, Stearns V, Jacobs L, Habibi M, Lange J, Hurley PJ, Lauring J, VandenBerg D, Kessler J, Jeter S, Samuels ML, Maar D, Cope L, Cimino-Mathews A, Argani P, Wolff AC,Park BH. Detection of cancer specific mutations in plasma of early stage breast cancer patients. Clin Cancer Res. 2014 May;20(10):2643-50.
  13. Jelovac D, Beaver JA, Balukrishna S, Wong HY, Toro PV, Cimino-Mathews A, Argani P, Stearns V, Jacobs L, VanDenBerg D, Kessler J, Jeter S, Park BH, Wolff AC. A PIK3CA mutation detected in plasma from a patient with synchronous primary breast and lung cancers. Human Pathol. 2014 Apr;45(4):880-3.
  14. Cimino-Mathews A, Ye X, Meeker A, Argani P, Emens LA. Metastatic Triple Negative Breast Cancers at First Relapse Have Fewer Tumor-Infiltrating Lymphocytes Than Their Matched Primary Breast Tumors: A Pilot Study. Human Pathol. 2013 Oct;44:2055-63
  15. Vandenbussche CJ, Elwood H, Cimino-Mathews A, Bittar Z, Illei PB, Warzecha HN. Clinicopathologic features of ductal carcinoma in situ in young women with an emphasis on molecular subtype. Hum Pathol. 2013 Nov;44:2487-93
  16. Cimino-Mathews A, Hicks JL, Sharma R, Vang R, Illei PB, De Marzo A, Emens LA, Argani P. A Subset of Malignant Phyllodes Tumors Harbors Alterations in the Rb/p16 Pathway. Human Pathol. 2013 Nov;44(11):2494-500.
  17. VandenBussche CJ, Khouri N, Sbaity E, Tsangaris TN, Vang R, Tatsas A, Cimino-Mathews A, Argani P. Borderline atypical duct hyperplasia/low grade ductal carcinoma in situ on breast needle core biopsy should be managed conservatively. Am J Surg Pathol. 2013 Jun; 37:913-23.
  18. Cimino-Mathews A, Ye X, Meeker A, Argani P, Emens LA. Metastatic Triple Negative Breast Cancers at First Relapse Have Fewer Tumor-Infiltrating Lymphocytes Than Their Matched Primary Breast Tumors: A Pilot Study. Human Pathol. 2013 Oct;44:2055-63.
  19. Cimino-Mathews A, Subhawong AP, Illei PB, Sharma R, Halushka MK, Vang R, Fetting JH, Park BH, Argani PA. GATA-3 Expression in Breast Carcinoma: Utility in Triple Negative, Sarcomatoid and Metastatic Carcinomas. Human Pathol. 2013 Jul;44:1341-9.
  20. Cimino-Mathews A, Subhawong AP, Elwood H, Warzecha HN, Sharma R, Park BH, Taube JM, Illei PB, Argani P. Neural crest transcription factor Sox10 is preferentially expressed in triple-negative and metaplastic breast carcinomas. Human Pathol. 2013 Jun;44(6):959-65.
  21. Garay JP, Karakas B, Abukhdeir AM, Cosgrove DP, Gustin JP, Higgins MJ, Konishi H, Konishi Y, Lauring J, Mohseni M, Wang GM, Jelovac D, Weeraratna A, Sherman Baust CA, Morin PJ, Toubaji A, Meeker A, De Marzo AM, Lewis G, Subhawong A, Argani P, Park BH. The growth response to androgen receptor signaling in ERα-negative human breast cells is dependent on p21 and mediated by MAPK activation. Breast Cancer Res. 2012 Feb 9;14(1):R27.
  22. Cimino-Mathews A, Hicks JL, Illei PB, Halushka MK, Fetting JH, De Marzo AM, Park BH, Argani P. Androgen receptor expression is usually maintained in initial surgically resected breast cancer metastases but is often lost in end-stage metastases found at autopsy. Human Pathology. 2012;43(7):1003-11.
    Recipient of Johns Hopkins Pathology Young Investigator's Day Award, Excellence in Clinical Research 2011
  23. Singhi AD, Cimino-Mathews A, Jenkins RB, Lan F, Fink SR, Nassar H, Vang R, Fetting JH, Hicks J, Sukumar S, De Marzo AM, Argani P. MYC gene amplification is often acquired in lethal distant breast cancer metastases of unamplified primary tumors. Mod Pathol. 2012;25(3):378-87.
  24. Heaphy CM, Subhawong AP, Hong SM, Goggins MG, Montgomery EA, Gabrielson E, Netto GJ, Epstein JI, Lotan TL, Westra WH, Shih IeM, Iacobuzio-Donahue CA, Maitra A, Li QK, Eberhart CG, Taube JM, Rakheja D, Kurman RJ, Wu TC, Roden RB, Argani P, De Marzo AM, Terracciano L, Torbenson M, Meeker AK. Prevalence of the alternative lengthening of telomeres telomere maintenance mechanism in human cancer subtypes. Am J Pathol. 2011 Oct;179(4):1608-15.
    Recipient of United States & Canadian Academy of Pathology Stowell-Orbison Award, 2011
  25. Konishi H, Mohseni M, Tamaki A, Garay JP, Croessmann S, Karnan S, Ota A, Wong HY, Konishi Y, Karakas B, Tahir K, Abukhdeir AM, Gustin JP, Cidado J, Wang GM, Cosgrove D, Cochran R, Jelovac D, Higgins MJ, Arena S, Hawkins L, Lauring J, Gross AL, Heaphy CM, Hosokawa Y, Gabrielson E, Meeker AK, Visvanathan K, Argani P, Bachman KE, Park BH. Mutation of a single allele of the cancer susceptibility gene BRCA1 leads to genomic instability in human breast epithelial cells. Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):17773-8.
  26. Lewis GH, Subhawong AP, Nassar H, Vang R, Illei PB, Park BH, Argani P. Relationship between molecular subtype of invasive breast carcinoma and expression of gross cystic disease fluid protein 15 and mammaglobin. Am J Clin Pathol. 2011 Apr;135(4):587-91.
  27. Heaphy CM, Subhawong AP, Gross AL, Konishi Y, Kouprina N, Argani P, Visvanathan K, Meeker AK. Shorter telomeres in luminal B, HER-2 and triple-negative breast cancer subtypes. Mod Pathol. 2011 Feb;24(2):194-200.
  28. Nassar H, Elieff MP, Kronz JD, Argani P. Pseudoangiomatous stromal hyperplasia (PASH) of the breast with foci of morphologic malignancy: a case of PASH with malignant transformation? Int J Surg Pathol. 2010 Dec;18(6):564-9.
  29. Cimino A, Halushka M, Illei P, Wu X, Sukumar S, Argani P. Epithelial cell adhesion molecule (EpCAM) is overexpressed in breast cancer metastases. Breast Cancer Res Treat. 2010 Oct;123(3):701-8.
  30. Subhawong AP, Nassar H, Halushka MK, Illei PB, Vang R, Argani P. Heterogeneity of Bcl-2 expression in metastatic breast carcinoma. Mod Pathol. 2010 Aug;23(8):1089-96.
  31. Subhawong AP, Subhawong TK, Khouri N, Tsangaris T, Nassar H. Incidental minimal atypical lobular hyperplasia on core needle biopsy: correlation with findings on follow-up excision. Am J Surg Pathol. 2010 Jun;34(6):822-8.
    Recipient of Johns Hopkins Pathology Young Investigator’s Day Award, Excellence in Clinical Research 2010
  32. Wu JM, Halushka MK, Argani P. Intratumoral heterogeneity of HER-2 gene amplification and protein overexpression in breast cancer. Hum Pathol. 2010 Jun;41(6):914-7.
  33. Subhawong AP, Heaphy CM, Argani P, Konishi Y, Kouprina N, Nassar H, Vang R, Meeker AK. The alternative lengthening of telomeres phenotype in breast carcinoma is associated with HER-2 overexpression. Mod Pathol. 2009 Nov;22(11):1423-31.
    Recipient of Johns Hopkins Pathology Young Investigator's Day Award, Excellence in Clinical Research 2009
  34. Nassar H, Sharafaldeen B, Visvanathan K, Visscher D. Ductal carcinoma in situ in African American versus Caucasian American women: analysis of clinicopathologic features and outcome. Cancer. 2009 Jul 15;115(14):3181-8.
  35. Subhawong AP, Subhawong T, Nassar H, Kouprina N, Begum S, Vang R, Westra WH, Argani P. Most basal-like breast carcinomas demonstrate the same Rb-/p16+ immunophenotype as the HPV-related poorly differentiated squamous cell carcinomas which they resemble morphologically. Am J Surg Pathol. 2009 Feb;33(2):163-75.
    Recipient of Johns Hopkins Pathology Young Investigator's Day Award, Excellence in Clinical Research, 2008
  36. Wu JM, Fackler MJ, Halushka MK, Molavi DW, Taylor ME, Teo WW, Griffin C, Fetting J, Davidson NE, De Marzo AM, Hicks JL, Chitale D, Ladanyi M, Sukumar S, Argani P. Heterogeneity of breast cancer metastases: comparison of therapeutic target expression and promoter methylation between primary tumors and their multifocal metastases. Clin Cancer Res. 2008 Apr 1;14(7):1938-46.
    Recipient of United States & Canadian Academy of Pathology Stowell-Orbison Award, 2007
  37. Cao D, Tsangaris TN, Kouprina N, Wu LS, Balch CM, Vang R, Argani P. The superficial margin of the skin-sparing mastectomy for breast carcinoma: factors predicting involvement and efficacy of additional margin sampling. Ann Surg Oncol. 2008 May;15(5):1330-40.
  38. Cao D, Polyak K, Halushka MK, Nassar H, Kouprina N, Iacobuzio-Donahue C, Wu X, Sukumar S, Hicks J, De Marzo A, Argani P. Serial analysis of gene expression of lobular carcinoma in situ identifies down regulation of claudin 4 and overexpression of matrix metalloproteinase 9. Breast Cancer Res. 2008;10(5):R91.