Genetic Counseling in the Follow-up of Breast Cancer patients; Conversion of a Luminal Tumor to TNBC

Main Article Content

Hamid Ahmadi
Reza Hosseinpour
Behnaz Jahanbin
Keivan Majidzadeh-A
Farid Azmoudeh-Ardalan


Breast Cancer, Genetic counseling, Triple negative, IHC, Conversion


Background: Triple-negative subtype does not have any of the receptors that are commonly found in breast cancer. Patients suffering from Triple-negative breast cancer are at risk of early metastasis and BRCA mutation. The conversion of the receptors during the metastatic progression or local recurrence of breast cancer is a well-known topic that affects the therapeutic measures and outcome. Confirmation of immunohistochemistry is essential in these conditions, but genetic evaluation is controversial.
Case presentation: A woman suffering from primary luminal breast cancer presented with femoral bone metastasis in the follow-up after two years. Bone metastasis was compatible with the triple-negative subtype. This case was discussed at the weekly breast multidisciplinary team session of the Department of Breast Surgery, Tehran University of Medical Sciences.
Question: Does the patient need genetics counseling in a conversion setting? And does the new specimen need CISH/FISH techniques to confirm TNBC tumors?
Conclusion: There are no strong guidelines to recommend genetic counseling and BRCA testing for patients with breast cancer biomarkers conversion. Re-assessing the specimen for ER, PR, and HER-2 is necessary for this setting.


1. Woo JW, Chung YR, Ahn S, Kang E, Kim E-K, Kim SH, et al. Changes in Biomarker Status in Metastatic Breast Cancer and Their Prognostic Value. J Breast Cancer. 2019;22(3):439-52.
2. Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. New England journal of medicine. 2010;363(20):1938-48.
3. von Minckwitz G, Schneeweiss A, Loibl S, Salat C, Denkert C, Rezai M, et al. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. The lancet oncology. 2014;15(7):747-56.
4. Harbeck N. Neoadjuvant therapy in patients with triple negative and HER2 positive early breast cancer. The Breast. 2017;32:S18.
5. Network NCC. Genetic/familial High-Risk assessment: Breast, Ovary and pancratic (version 1.2020) [Available from:
6. Mersch J, Jackson MA, Park M, Nebgen D, Peterson SK, Singletary C, et al. Cancers associated with BRCA 1 and BRCA 2 mutations other than breast and ovarian. Cancer. 2015;121(2):269-75.
7. Dowdy SC, Stefanek M, Hartmann LC. Surgical risk reduction: prophylactic salpingo-oophorectomy and prophylactic mastectomy. American journal of obstetrics and gynecology. 2004;191(4):1113-23.
8. Calderon?Margalit R, Paltiel O. Prevention of breast cancer in women who carry BRCA1 or BRCA2 mutations: a critical review of the literature. International journal of cancer. 2004;112(3):357-64.
9. Nguyen TH, Nguyen VH, Nguyen TL, Qiuyin C, Phung TH. Evaluations of Biomarker Status Changes between Primary and Recurrent Tumor Tissue Samples in Breast Cancer Patients. BioMed research international. 2019;2019.
10. Cejalvo JM, de Dueñas EM, Galván P, García-Recio S, Gasión OB, Paré L, et al. Intrinsic subtypes and gene expression profiles in primary and metastatic breast cancer. Cancer research. 2017;77(9):2213-21.
11. Allred DC. Commentary: hormone receptor testing in breast cancer: a distress signal from Canada. Oncologist. 2008;13(11):1134-6.
12. de Dueñas EM, Hernández AL, Zotano ÁG, Carrión RMP, López-Muñiz JIC, Novoa SA, et al. Prospective evaluation of the conversion rate in the receptor status between primary breast cancer and metastasis: results from the GEICAM 2009-03 ConvertHER study. Breast cancer research and treatment. 2014;143(3):507-15.
13. Amir E, Clemons M, Purdie CA, Miller N, Quinlan P, Geddie W, et al. Tissue confirmation of disease recurrence in breast cancer patients: pooled analysis of multi-centre, multidisciplinary prospective studies. Cancer treatment reviews. 2012;38(6):708-14.
14. Kuukasjärvi T, Karhu R, Tanner M, Kähkönen M, Schäffer A, Nupponen N, et al. Genetic heterogeneity and clonal evolution underlying development of asynchronous metastasis in human breast cancer. Cancer research. 1997;57(8):1597-604.
15. Stefanovic S, Wirtz R, Deutsch TM, Hartkopf A, Sinn P, Varga Z, et al. Tumor biomarker conversion between primary and metastatic breast cancer: mRNA assessment and its concordance with immunohistochemistry. Oncotarget. 2017;8(31):51416-28.
16. Fabi A, Di Benedetto A, Metro G, Perracchio L, Nisticò C, Di Filippo F, et al. HER2 protein and gene variation between primary and metastatic breast cancer: significance and impact on patient care. Clinical Cancer Research. 2011;17(7):2055-64.
17. Holdaway I, Bowditch J. Variation in receptor status between primary and metastatic breast cancer. Cancer. 1983;52(3):479-85.
18. Rasmussen BB, Kamby C. Immunohistochemical detection of estrogen receptors in paraffin sections from primary and metastatic breast cancer. Pathology-Research and Practice. 1989;185(6):856-9.
19. Kuukasjärvi T, Kononen J, Helin H, Holli K, Isola J. Loss of estrogen receptor in recurrent breast cancer is associated with poor response to endocrine therapy. Journal of Clinical Oncology. 1996;14(9):2584-9.
20. Lower EE, Glass EL, Bradley DA, Blau R, Heffelfinger S. Impact of metastatic estrogen receptor and progesterone receptor status on survival. Breast cancer research and treatment. 2005;90(1):65-70.
21. Broom RJ, Tang PA, Simmons C, Bordeleau L, Mulligan AM, O'MALLEY FP, et al. Changes in estrogen receptor, progesterone receptor and Her-2/neu status with time: discordance rates between primary and metastatic breast cancer. Anticancer research. 2009;29(5):1557-62.
22. Simmons C, Miller N, Geddie W, Gianfelice D, Oldfield M, Dranitsaris G, et al. Does confirmatory tumor biopsy alter the management of breast cancer patients with distant metastases? Annals of oncology. 2009;20(9):1499-504.
23. Amir E, Ooi W, Simmons C, Kahn H, Christakis M, Popovic S, et al. Discordance between receptor status in primary and metastatic breast cancer: an exploratory study of bone and bone marrow biopsies. Clinical oncology. 2008;20(10):763-8.
24. Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clinical cancer research. 2007;13(15):4429-34.
25. Cleator S, Heller W, Coombes RC. Triple-negative breast cancer: therapeutic options. The lancet oncology. 2007;8(3):235-44.

Article Statistics :Views : 481 | Downloads : 541

Most read articles by the same author(s)