Clinicopathological and immunohistochemical correlations of breast carcinoma with vitamin D status in Erbil Governorate, Kurdistan of Iraq

Sara Alaaldin Abdulrazzaq; Nadya Yassoub Ahmed

doi:10.15218/zjms.2020.008

Authors

Sara Alaaldin Abdulrazzaq Department of Pathology, College of Medicine, Hawler Medical University, Erbil, Iraq
Nadya Yassoub Ahmed Department of Pathology, College of Medicine, Hawler Medical University, Erbil, Iraq

DOI:

https://doi.org/10.15218/zjms.2020.008

Keywords:

Breast cancer, Molecular types, Vitamin D

Abstract

Background and objective: Vitamin D has been associated with decreased risk of several cancers, including breast cancer, and its deficiency has been associated with poor prognosis. This study evaluated vitamin D level in breast cancer patients at diagnosis and investigated its association with various breast cancer prognostic criteria, especially the intrinsic molecular subtypes.

Methods: Using a prospective population-based, case-control and case series, study in Erbil city during 1^st October 2017 and 31^st March 2018, we evaluated vitamin D status in 50 breast cancer patients in correlation with 100 normal healthy controls. We examined various clinicopathological and immunohistochemical features of breast cancer to determine the prognostic effect of plasma 25-hydroxyvitamin D levels at diagnosis.

Results: The mean patient’s age was 51.1±10.7 years. The mean plasma 5-hydroxyvitamin D concentration was 8.138 ±7.5 and 16.7±12.06ng/mL in the breast cancer patients and controls, respectively (P <0.001). Vitamin D deficiency was associated with positive breast cancer risk (Odds Ratio (OR), 4.1; 95% confidence interval (CI), 1.68–10). The risk was greater in premenopausal (OR=7.5; 95%CI =1.60-35.23) than postmenopausal women (OR=2.7; 95%CI =0.87- 8.49). The mean serum level of 5-hydroxyvitamin D decreased significantly with the increasing stage in premenopausal (P = 0.055) and HER2/neu +ve immunoexpression (P = 0.008), especially in postmenopausal (P = 0.035). Regarding the molecular subtypes, HER2/neu enriched type showed the lowest mean 5-hydroxyvitamin D with a significant statistical association in premenopausal (P = 0.033).

Conclusion: These results add to a growing body of evidence that vitamin D deficiency associated with breast cancer risk and prognosis. Well-designed clinical trials are highly needed to determine whether vitamin D supplementation is effective for breast cancer chemoprevention and prognosis improvement if occur.

Keywords: Breast cancer; Molecular types; Vitamin D.

Metrics

Metrics Loading ...

References

Siegel RL, Miller KD, Jemal A. Cancer statistics. CA Cancer J Clin 2016; 66:7–30.

Alwan N. Iraqi Initiative of a Regional Comparative Breast Cancer Research Project in the Middle East. J Cancer Biol Res 2014; 2(1):1016.

Othman RT, Abdulljabar R, Saeed A, Kittani SS, Sulaiman HM, Mohammed SA, et al. Cancer incidence rates in the Kurdistan region/Iraq from 2007-2009. Asian Pac J Cancer Prev 2011; 12(5):1261–4.

Haq A, Sofi NY. Vitamin D and breast cancer: Indian prespective. Clinical Nutrition Experimental 2017; 12:1–10.

Crew KD, Gammon MD, Steck SE, Hershman DL, Cremers S, Dworakowski E, et al. Association between plasma25- hydroxyvitamin D & breast cancer risk. Cance Prev Res 2009; 2(6):598–604.

Garland CF, Gorham ED, Mohr SB, Garland FC. Vitamin D for cancer prevention: Global perspective. Ann Epidemiol 2009; 19:468–83.

Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Viatmin D and calcium supplementation reduces cancer risk: Results of a randomized trial. Am Clin Nutr 2007; 85:1586–91.

Imtiaz S, Siddiqui N, Raza SA, Loya A, Muhammad A. Vitamin D deficiency in newly diagnosed breast cancer patients. Indian J Endocrinol Metab 2012; 16(3): 409–13.

Elizabeth R, Bertone-Johnson SD. Vitamin D and Breast Cancer. Ann Epidemiol 2009; 19(7):462–7.

Colston KW, Hansen CM. Mechanisms implicated in the growth regulatory effects of vitamin D in breast cancer. Endocr Relat Cancer 2002; 9:45–59.

Palmieri C, MacGregor T, Girgis S, Vigushin D. Serum 25-hydroxyvitamin D levels in early and advanced breast cancer. J Clin Pathol 2006; 59(12):1334–6.

Edge SB, Compton CC. The American Joint Committee on Cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010; 17:1471–4.

Pradhan A, Paudyal P, Sinha AK, Agrawal CS. Grading, staging and Nottingham prognostic index scoring of breast carcinoma. Journal of Pathology of Nepal 2017; 7:1078–83.

Hammond ME, Hayes DF, Dowestt M, Allred DC, Hagerty KL, Badve S, et al. 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.

Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thutlimann B, Senn HJ, et al. Strategies for subtyped of dealing with the diversity of breast cancer–highlights of the St. Gallen International Expert Consensus on the primary therapy of early breast cancer 2011. Ann Oncol 2011; 22(8):1736–47.

Ringe JD, Kipshoven C. Vitamin D-insufficiency: An estimate of the situation in Germany. Dermato-endocrinology 2012; 4(1):72–80.

Colston KW. Vitamin D and breast cancer risk. Best Pract Res Clin End Met 2008; 22:587–99.

Moukayed M, Grant WB. Molecular link between vitamin D and cancer prevention. Nutrition 2013; 5(10):3993–4021.

Welsh J. Vitamin D and breast cancer: insights from animal models. Am J Clin Nutr 2004; 80:1721S–4S.

Khan QJ, Kimler BF, Fabian CJ. The relationship between vitamin D and breast cancer incidence and natural history. Curr Oncol Rep 2010; 12:136–42.

Al-Hilali K A. Prevalence of Hypovitaminosis D in Adult Iraqi People Including Postmenopausal Women. SCIRJ 2016; 4(9):53–62.

Yousef FM, Jacobs ET, Kang PT, Hakim IA, Going S, Yousef JM, et al. Vitamin D status and breast cancer in Saudi Arabian women: case–control study. Am J Clin Nutr 2013; 98:105–10.

Arabi A, El Rassi R, El-Hajj Fuleihan G. Hypo-vitaminosis D in developing countries-prevalence, risk factors and outcomes. Nat Rev Endocrinol 2010; 6(10):550–61.

Spiro A, Buttriss J L. An overview of Vitamin D status and intake in Europe. Nutr Bull 2014; 39(4):322–50.

El-Shorbagy S, Haggag R, Ebian HF, Labib HA, Harb OA. Prognostic Impact of 25-Hydroxyvitamin D Levels in Egyptian Patients with Breast Cancer. J Cancer Sci Ther 2017; 9:496–502.

Khan QJ, Fabian CJ. How I treat vitamin D Deficiency. JOP 2010; 6:97–100.

Yin L, Grandi N, Raum E. Meta-analysis: Serum vitamin D and breast cancer risk. Eur J Cancer 2010; 64(12):2196–205.

Vrieling A, Hein R, Abbas S, Schneeweiss A, Flesch-Janys D, Chang-Claude J. Serum 25-hydroxy vitamin D and postmenopausal breast cancer survival: A prospective patient cohort study. Breast Cancer Res 2011; 13(4):R74.

Napoli N, Vattikuti S, Ma C, Rastelli A, Rayani A, Donepudi R, et al. High prevalence of low vitamin D and musculoskeletal complaints in women with breast cancer. Breast J 2010; 16:609–16.

Camacho PM, Dayal AS, Diaz JL, Nabhan FA, Agarwal M, Norton JG, et al. Prevalence of secondary causes of bone loss among breast cancer patients with osteopenia and osteoprosis. J Clin Oncol 2008; 26:5380–5.

Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire RL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987; 235:177–82.

Smail A, El-Awady R, Mohamed G, Hussein M, Ramadan SS. Prognostic Significance of Serum Vitamin D Levels in Egyptian Females with Breast cancer. Asian Pac J Cancer Prev 2018 26; 19(2):571–6.

Lukong KE. Understanding breast cancer – The long and winding road. BBA Clinical 2017; 7:64–77.

Kim HJ, Lee YM, Ko BS, Lee JW, Yu JH, Son BH, et al. Vitamin D deficiency is correlated with poor outcomes in patients with luminal type breast cancer. Ann Surg Oncol 2011; 18:1830–6.

Blackmore KM, Lesosky M, Barnett H, Raboud JM, Vieth R, Knight JA. Vitamin D from dietary intake and sunlight exposure and the risk of hormone-receptor-defined breast cancer. Am J Epidemiol 2008; 168(8):915–24.

McCullough ML, Rodriguez C, Diver WR, Feigelson HS, Stevenes VL, Thun MJ, et al. Dairy, calcium, and vitamin D intake and postmenopausal breast cancer risk in the Cancer Prevention Study II Nutrition Cohort. Cancer Epidemiol Biomarkers Prevent 2005; 14(12):2898–904.

Kawase T, Matsuo K, Suzuki T, Hirose K, Hosono S, Watanabe A, et al. Association between vitamin D and calcium intake and breast cancer risk according to menopausal status and receptor status in Japan. Cancer Sci 2010; 101(5):1234–40.