BREAST CANCER IN WOMEN YOUNGER THAN 35 YEARS OLD: IMMUNOHISTOCHEMICAL AND MOLECULAR CHARACTERISTICS AND IMAGING DIAGNOSIS
Keywords:
BREAST CANCER, YOUNG WOMEN, AGE, LUMINALAbstract
The aim of this study was to characterize imaging, immunohistochemical and molecular breast cancer in women younger than 35 years old. Material and methods: In this retrospective study, data were collected from 46 patients under the age of 35, out of a total of 1,854 patients diagnosed with breast cancer between May 2012 and February 2019 at the Regional Institute of Oncology Iasi (Department of Surgery). The following tumor characteristics were evaluated: tumor size, histological type, molecular subtype, histological grade, nodal status and the presence of systemic metastases. Results: Of the 46 cases, invasive ductal carcinoma was the most common histological type (n=31, 67.39%). More than half of the tumors were ER + (n=36, 78.26%) and PR + (n=33, 71.73%). In 84.78% of cases (n=39) we observed a high expression of Ki67 proliferation index (> 20%). Luminal genomic B subtype was the most common (n=27, 58.69%), and triple negative breast cancer was 13.04% (n=6). Conclusions: Breast tumors in young women (under the age of 35) have a much more aggressive tumor biology. Future research is required to investigate new treatment strategies especially in young breast cancer patients.
References
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39. Shim HJ, Kim SH, Kang BJ, et al. Breast cancer recurrence according to molecular subtype. Asian Pac J Cancer Prev 2014; 15(14): 5539-5544.
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49. Fitzgibbons PL, Page DL, Weaver D, et al. Prognostic Factors in Breast Cancer. Arch Pathol Lab Med 2000; 124: 13.
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55. Dunnwald LK, Rossing MA, Li CI. Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients. Breast Cancer Res 2007; 9(1): R6.
56. Foulkes WD, Reis-Filho JS, Narod SA. Tumor size and survival in breast cancer - a reappraisal. Nat Rev Clin Oncol 2010; 7: 348-353.
57. Curigliano G, Viale G, Bagnardi V, et al. Clinical relevance of HER2 over expression/ amplification in patients with small tumor size and node-negative breast cancer. J Clin Oncol 2009; 27: 5693-5699.
58. Curigliano G1, Viale G, Bagnardi V, et al. Tumor size is an unreliable predictor of prognosis in basal-like breast cancers and does not correlate closely with lymph node status. Breast Cancer Res Treat. 2009; 117:199-204.
59. Gonzalez-Angulo AM, Litton JK, et al. 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 2009; 27: 5700-5706.
2. Furtunescu F, Bohiltea R, Voinea S, et al. Breast cancer mortality gaps in Romanian women com-pared to the EU after 10 years of accession: Is breast cancer screening a priority for action in Romania? (Review of the Statistics). Exp Ther Med 2021; 21(3): 268.
3. Tofan M, Brătucu G, Chițu IB, Dovleac L. Romania’s breast cancer and healthcare education. 2018;3(2):7.
4. Ayadi L, Khabir A, Amouri H, et al. Correlation of HER-2 over-expression with clinico-pathological parameters in Tunisian breast carcinoma. World J Surg Onc 2008; 6(1): 112.
5. Sohail SK, Sarfraz R, Imran M, Kamran M, Qamar S. Estrogen and Progesterone Receptor Expres-sion in Breast Carcinoma and Its Association With Clinicopathological Variables Among the Paki-stani Population. Cureus [Internet]. 2020 August 14 [cited 2022 July 7]; Available from: https://www.cureus.com/articles/37910-estrogen-and-progesterone-receptor-expression-in-breast-carcinoma-and-its-association-with-clinicopathological-variables-among-the-pakistani -population
6. Barbareschi M, Doglioni C. The immunohistochemical detection of steroid hormone receptors in breast cancer: open problems and new perspectives. Pathologica 2002; 94: 115-120.
7. Rosenberg LU, Magnusson C, Lindstrom E, Wedren S, Hall P, Dickman PW. Menopausal hormone therapy and other breast cancer risk factors in relation to the risk of different histological subtypes of breast cancer: a case control study. Breast Cancer Res 2006; 8: R11.
8. Kurosumi M. Immunohistochemical assessment of hormone receptor status using a new scoring system (J-Score) in breast cancer. Breast Cancer 2007; 14: 189-193.
9. Zheng YZ, Wang L, Hu X, Shao ZM. Effect of tumor size on breast cancer-specific survival stratified by joint hormone receptor status in a SEER population-based study. Oncotarget 2015; 6(26): 22985-22995.
10. Goldhirsch A, Glick JH, Gelber RD, Coates AS, Thürlimann B, Senn HJ. Panel members. Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005. Ann Oncol. 2005; 16: 1569-1583.
11. Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver MJ. World Health Organization (WHO) classification of tumors of the breast. 4th edition, WHO Classification of Tumors, International Agency for Research on Cancer (IARC) Press, Lyon, France, 2014, 203-231.
12. Brierley JD, Gospodarowicz MK, Wittekind C. TNM classification of malignant tumors, 8th edition, John Wiley & Sons. 2016.
13. Perou CM, Sørlie T, Eisen MB, et al. Molecular portraits of human breast tumors. Nature 2000; 406(6797): 747-752 / doi: 10.1038/35021093.
14. Allred DC, Harvey JM, Berardo M, Clark GM. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 1998; 11(2): 155-168.
15. Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology; College of American Pathologists. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med 2010; 134(7): e48-72 / doi: 10.5858/ 134. 7.e48.
16. Canas-Marques R, Schnitt SJ. E-cadherin immunohistochemistry in breast pathology uses and pitfalls. Histopathology 2016; 68(1): 57-69 / doi: 10.1111/his.12869.
17. Dowsett M, Nielsen TO, A’Hern R, et al. International Ki-67 in Breast Cancer Working Group. Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer working group. J Natl Cancer Inst. 2011; 103(22): 1656-1664 /doi: 10.1093/jnci/djr393.
18. Brenner DR, Brockton NT, Kotsopoulos J, et al. Breast cancer survival among young women: a review of the role of modifiable lifestyle factors. Cancer Causes Control 2016; 27(4): 459-472.
19. Madden JL, Kandalaft S, Bourque RA. Modified radical mastectomy. Ann Surg 1972; 175(5): 624-634 / doi: 10.1097/00000658-197205000-00002.
20. Brinton LA, Sherman ME, Carreon JD, Anderson WF. Recent trends in breast cancer among younger women in the United States. J Natl Cancer Inst. 2008; 100(22): 1643-1648 / doi: 10.1093/jnci/djn344.
21. Meng J. Clinical analysis for young female patients with breast cancer. Chinese J Clin Oncol 2006; 33: 1316-1319.
22. Walker RA, Lees E, Webb MB, Dearing SJ. Breast carcinomas occurring in young women (<35 years) are different. Br J Cancer 1996; 74: 1796-1800.
23. Han W, Kim SW, Park IA, et al. Young age: an independent risk factor for disease-free survival in women with operable breast cancer. BMC Cancer 2004; 17(4): 82.
24. Fredholm H, Magnusson K, Lindström LS, et al. Long-term outcome in young women with breast cancer: a population-based study. Breast Cancer Res Treat 2016; 160(1): 131-143.
25. Chen HL, Zhou MQ, Tian W, Meng KX, He HF. Effect of age on breast cancer patient prognoses: a population-based study using the SEER 18 database. PLoS One 2016; 11(10): e0165409.
26. Erić I. Breast Cancer in Young Women: Pathologic and Immunohistochemical Features. ACC [Internet]. 2018 [cited 2022 July 9]; Available from: https://hrcak.srce.hr/index.php? show=clanak &id_ clanak_jezik=315417
27. Bertheau P, Steinberg SM, Cowan K, Merino MJ. Breast cancer in young women: clinicopathologic correlation. Semin Diagn Pathol 1999; 16(3): 248-256.
28. Copson E, Eccles B, Maishman T, et al. Prospective observational study of breast cancer treatment outcomes for UK women aged 18-40 years at diagnosis: the POSH study. J Natl Cancer Inst. 2013, 105, 978-988.
29. Singh R, Gupta S, Pawar SB, Pawar RS, Gandham SV, Prabhudesai S. Evaluation of ER, PR and HER-2 receptor expression in breast cancer patients presenting to a semi urban cancer centre in Western India. J Can Res Ther 2014; 10: 26-28.
30. Nabi MG, Ahangar A, Kaneez S: Estrogen receptors, progesterone receptors and their correlation with respect to HER-2/neu status, histological grade, size of lesion, lymph node metastasis, lymphovascular involvement and age in breast cancer patients in a hospital in north India. Asian J Med Sci 2016; 7: 34.
31. Mahmoud MM: Breast cancer in Kirkuk City, hormone receptors status (estrogen and progesterone) and Her-2/Neu and their correlation with other pathologic prognostic variables. DJM 2014; 1: 1-14.
32. Zubair M, Khadim MT, Tariq H, Ali S, Khan OA, Gul S. Immunohistochemical and clinicopathological factors associated with axillary lymph node metastasis in breast cancer patients of Northern Pakistan. Asian Pac J Cancer Care 2017; 4: 67-71.
33. Hashmi AA, Aijaz S, Khan SM, et al. Prognostic parameters of luminal A and luminal B intrinsic breast cancer subtypes of Pakistani patients. World J Surg Oncol 2018; 16(1): 1.
34. Dayal A, Shah RJ, Kothari S, Patel SM. Correlation of Her-2/neu status with estrogen, progesterone receptors and histologic features in breast carcinoma. APALM 2016, 3: 476-483.
35. Patanaphan V, Salazar OM, Risco R. Breast cancer: metastatic patterns and their prognosis. South Med J 1988; 81(9): 1109-1112.
36. Agrup M, Stål O, Olsen K, Wingren S. C-erbB-2 overexpression and survival in early onset breast cancer. Breast Cancer Res Treat 2000; 63(1): 23-29.
37. Anders CK, Hsu DS, Broadwater G, et al. Young age at diagnosis correlates with worse prognosis and defi nes a subset of breast cancers with shared patterns of gene expression. J Clin Oncol 2008; 26: 3324-3330.
38. Ribnikar D, Ribeiro JM, Pinto D, et al. Breast Cancer Under Age 40: a Different Approach. Curr Treat Options in Oncol 2015; 16(4): 16 / doi: 10.1007/s11864-015-0334-8.
39. Shim HJ, Kim SH, Kang BJ, et al. Breast cancer recurrence according to molecular subtype. Asian Pac J Cancer Prev 2014; 15(14): 5539-5544.
40. Laible M, Hartmann K, Gürtler C, et al. Impact of molecular subtypes on the prediction of distant recurrence in estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) negative breast cancer upon five years of endocrine therapy. BMC Cancer 2019; 19(1): 694.
41. Azim Jr HA, Michiels S, Bedard PL, et al. Elucidating prognosis and biology of breast cancer arising in young women using gene expression profiling. Clin Cancer Res 2012; 18: 1341-1351.
42. Bouferraa Y, Haibe Y, Chedid A, et al. The impact of young age (< 40 years) on the outcome of a cohort of patients with primary non-metastatic breast cancer: analysis of 10-year survival of a prospective study. BMC Cancer 2022; 22(1): 27.
43. Fredholm H, Magnusson K, Lindström LS, et al. Breast cancer in young women and prognosis: How important are proliferation markers? European Journal of Cancer 2017; 84: 278-89.
44. Goldhirsch A, Winer EP, Coates AS, et al. 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. Ann Oncol 2013; 24(9): 2206-2223.
45. Carvalho FM, Bacchi LM, Santos PP, Bacchi CE. Triple-negative breast carcinomas are a heterogeneous entity that differs between young and old patients. Clinics(Sao Paulo) 2010; 65(10): 1033-1036.
46. Iqbal B, Buch A. Hormone receptor (ER, PR, HER2/neu) status and proliferation index marker (Ki-67) in breast cancers: Their onco-pathological correlation, shortcomings and future trends. Med J DY Patil Univ 2016; 9(6): 674.
47. Luporsi E, André F, Spyratos F, et al. Ki-67: Level of evidence and methodological considerations for its role in the clinical management of breast cancer: Analytical and critical review. Breast Cancer Res Treat 2012; 132: 895-915.
48. Colozza M, Sidoni A, Piccart-Gebhart M. Value of Ki67 in breast cancer: The debate is still open. Lancet Oncol 2010; 11: 414-415.
49. Fitzgibbons PL, Page DL, Weaver D, et al. Prognostic Factors in Breast Cancer. Arch Pathol Lab Med 2000; 124: 13.
50. Mirza AN, Mirza NQ, Vlastos G, Singletary SE. Prognostic Factors in Node-Negative Breast Cancer. Ann Surg 2002; 235(1): 17.
51. Singletary SE, Allred C, Ashley P, et al. Revision of the American Joint Committee on Cancer staging system for breast cancer. J Clin Oncol. 2002; 20:3628-3636.
52. Greene FL, Fritz A, Balch CM. AJCC Cancer Staging Manual. 6. (Chicago, IL: Springer) 2002.
53. Boffa D J, Greene F L. Reacting to changes in staging designations in the 7th edition of the AJCC staging manual. Ann Surg Oncol 2011; 18: 1-3.
54. Anderson WF, Chu KC, Chatterjee N, Brawley O, Brinton LA. Tumor Variants by Hormone Receptor Expression in White Patients With Node-Negative Breast Cancer From the Surveillance, Epidemiology, and End Results Database. JCO 2001; 19(1): 18-27.
55. Dunnwald LK, Rossing MA, Li CI. Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients. Breast Cancer Res 2007; 9(1): R6.
56. Foulkes WD, Reis-Filho JS, Narod SA. Tumor size and survival in breast cancer - a reappraisal. Nat Rev Clin Oncol 2010; 7: 348-353.
57. Curigliano G, Viale G, Bagnardi V, et al. Clinical relevance of HER2 over expression/ amplification in patients with small tumor size and node-negative breast cancer. J Clin Oncol 2009; 27: 5693-5699.
58. Curigliano G1, Viale G, Bagnardi V, et al. Tumor size is an unreliable predictor of prognosis in basal-like breast cancers and does not correlate closely with lymph node status. Breast Cancer Res Treat. 2009; 117:199-204.
59. Gonzalez-Angulo AM, Litton JK, et al. 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 2009; 27: 5700-5706.
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