Molecular characteristics of breast cancer according to clinicopathological factors

Huszno,Joanna; Kolosza,Zofia

doi:10.3892/mco.2019.1869

Molecular characteristics of breast cancer according to clinicopathological factors

Authors:
- Joanna Huszno
- Zofia Kolosza
View Affiliations

Affiliations: I Radiation and Clinical Oncology Department, Maria Skłodowska‑Curie Memorial Cancer Center and Institute of Oncology, 44‑101 Gliwice, Poland, Biostatistic Unit, Maria Skłodowska‑Curie Memorial Cancer Center and Institute of Oncology, 44‑101 Gliwice, Poland
Published online on: May 28, 2019 https://doi.org/10.3892/mco.2019.1869
Pages: 192-200

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The purpose of the present study was to evaluate the correlation between molecular factors such as BRCA1 DNA repair associated (BRCA1), checkpoint kinase 2 (CHEK2) and nucleotide binding oligomerization domain containing 2 (NOD2) gene mutations and clinicopathological factors in patients with breast cancer (BC). Prognostic factors were analyzed in BC patients with confirmed BRCA1 (n=73), CHEK2 (n=51) and NOD2 (n=31) mutations. The control group was selected from BC patients without mutations (n=392). The BRCA‑associated cancer cases were significantly more often triple negative compared with sporadic cancer (62% vs. 14%; P=0.0001). Luminal B HER2‑positive and HER2‑positive non‑luminal subtypes were observed more often in the control group (33 and 17%). The luminal A subtype was detected in 53% of CHEK2 mutation carriers and 45% of NOD2 mutation carriers. A lower histological grade was observed significantly more often in patients with CHEK2 mutations in comparison with the control group (88 vs. 69%; P=0.003). Lymph nodes without metastases were reported more frequently in NOD2 mutation carriers (74 vs. 54%; P=0.038), in BRCA1 mutations (73 vs. 54%; P=0.004) and, although not significantly, in CHEK2 mutation carriers (69 vs. 54%; P=0.071) compared with the control group. In conclusion, BRCA1 mutation was associated with TNBC and the luminal B HER2 (‑) subtype. HER2‑positive subtypes were characteristic of the control group. CHEK2 and NOD2 mutation carriers had a more favorable profile of prognostic factors.

View Figures

View References

1	Yersal O and Barutca S: Biological subtypes of breast cancer: Prognostic and therapeutic implications. World J Clin Oncol. 10:412–424. 2014. View Article : Google Scholar
2	Brierley JD, Gospodarowicz MK and Wittekind C: TNM Classification of Malignant Tumours. 8th. Oxford; UK: Wiley Blackwell: 2017
3	Senkus E, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rutgers E, Zackrisson S and Cardoso F; ESMO Guidelines Committee, : Primary breast cancer: ESMO clinical practice guidelines. Ann Oncol. 26 (Suppl 5):v8–v30. 2015. View Article : Google Scholar : PubMed/NCBI
4	Nadji M, Gomez-Fernandez C, Ganjei-Azar P and Morales AR: Immuno-histochemistry of estrogen and progesterone receptors reconsidered: Experience with 5,993 breast cancers. Am J Clin Pathol. 123:21–27. 2005. View Article : Google Scholar : PubMed/NCBI
5	Ragab HM, Samy N, Afify M, Maksoud NA and Shaaban HM: Assessment of Ki-67 as a potential biomarker in patients with breast cancer. J Genet Engineering and Biotechnol. 16:479–484. 2018. View Article : Google Scholar
6	Gnant M, Thomssen C and Harbeck N: St. Gallen/Vienna 2015: A Brief summary of the consensus discussion. Breast Care (Basel). 10:124–130. 2015. View Article : Google Scholar : PubMed/NCBI
7	Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, Karaca G, Troester MA, Tse CK, Edmiston S, et al: Race, breast cancer subtypes, and survival in the Carolina breast cancer study. JAMA. 295:2492–24502. 2006. View Article : Google Scholar : PubMed/NCBI
8	Creighton CJ: The molecular profile of luminal B breast cancer. Biologics. 6:289–297. 2012.PubMed/NCBI
9	Hubalek M, Czech T and Müller H: Biological subtypes of triple-negative breast cancer. Breast Care (Basel). 12:8–14. 2017. View Article : Google Scholar : PubMed/NCBI
10	Godet I and Gilkes DM: BRCA1 and BRCA2 mutations and treatment strategies for breast cancer. Integr Cancer Sci Ther. 4:2017.PubMed/NCBI
11	Apostolou P and Papasotiriou I: Current perspectives on CHEK2 mutations in breast cancer. Breast Cancer (Dove Med Press). 9:331–335. 2017.PubMed/NCBI
12	Silwal-Pandit L, Vollan HK, Chin SF, Rueda OM, McKinney S, Osako T, Quigley DA, Kristensen VN, Aparicio S, Børresen-Dale AL, et al: TP53 mutation spectrum in breast cancer is subtype specific and has distinct prognostic relevance. Clin Cancer Res. 20:3570–3580. 2014. View Article : Google Scholar
13	Southey MC, Winship I and Nguyen-Dumont T: PALB2: Research reaching to clinical outcomes for women with breast cancer. Hered Cancer Clin Pract. 14:92016. View Article : Google Scholar : PubMed/NCBI
14	Huszno J, Nożyńska EZ, Lange D, Kołosza Z and Nowara E: The association of tumor lymphocyte infiltration with clinicopathological factors and survival in breast cancer. Pol J Pathol. 68:26–32. 2017. View Article : Google Scholar : PubMed/NCBI
15	Montagna E, Vingiani A, Maisonneuve P, Cancello G, Contaldo F, Pruneri G and Colleoni M: Unfavorable prognostic role of tumor-infiltrating lymphocytes in hormone-receptor positive, HER2 negative metastatic breast cancer treated with metronomic chemotherapy. Breast. 34:83–88. 2017. View Article : Google Scholar : PubMed/NCBI
16	Huszno J, Kołosza Z and Grzybowska E: BRCA1 mutation in breast cancer patients: Analysis of prognostic factors and survival. Oncol Lett. 17:1986–1995. 2019.PubMed/NCBI
17	Huszno J, Budryk M, Kołosza Z, Tęcza K, Pamuła Piłat J, Nowara E and Grzybowska E: A comparison between CHEK2*1100delC/I157T mutation carrier and noncarrier breast cancer patients: A clinicopathological analysis. Oncology. 90:193–198. 2016. View Article : Google Scholar : PubMed/NCBI
18	Huszno J, Kołosza K, Tęcza T, Pamuła-Piłat J, Mazur M and Grzybowska E: Comparison between NOD2 gene mutation carriers (3020insC) and non-carriers in breast cancer patients: A clinicopathological and survival analysis. AMS Civilization Dis. 3:10e–15e. 2018. View Article : Google Scholar
19	Triantafyllidou O, Vlachos IS, Apostolou P, Konstantopoulou I, Grivas A, Panopoulos C, Dimitrakakis C, Kassanos D, Loghis C, Bramis I, et al: Epidemiological and clinicopathological characteristics of BRCA-positive and BRCA-negative breast cancer patients in Greece. J BUON. 20:978–984. 2015.PubMed/NCBI
20	Kutomi G, Ohmura T, Suzuki Y, Kameshima H, Shima H, Takamaru T, Satomi F, Otokozawa S, Mori M and Hirata K: Clinicopathological characteristics of basal type breast cancer in triple-negative breast cancer. J Cancer Therapy. 3:836–840. 2012. View Article : Google Scholar
21	Evans DG, Lalloo F, Howell S, Verhoef S, Woodward ER and Howell A: Low prevalence of HER2 positivity amongst BRCA1 and BRCA2 mutation carriers and in primary BRCA screens. Breast Cancer Res Treat. 155:597–601. 2016. View Article : Google Scholar : PubMed/NCBI
22	Peshkin BN, Alabek ML and Isaacs C: BRCA1/2 mutations and triple negative breast cancers. Breast Dis. 32:25–33. 2010. View Article : Google Scholar : PubMed/NCBI
23	Huszno J, Budryk M, Kołosza Z and Nowara E: The influence of BRCA1/BRCA2 mutations on toxicity related to chemotherapy and radiotherapy in early breast cancer patients. Oncology. 85:278–82. 2013. View Article : Google Scholar : PubMed/NCBI
24	Kirova YM, Savignoni A, Sigal-Zafrani B, de La Rochefordiere A, Salmon RJ, This P, Asselain B, Stoppa-Lyonnet D and Fourquet A: Is the breast conserving treatment with radiotherapy appropriate in BRCA1/2 mutation carries? Long-term results and review of the literature. Breast Cancer Res Treat. 120:119–126. 2010. View Article : Google Scholar : PubMed/NCBI
25	de Bock GH, Mourits MJ, Schutte M, Krol-Warmerdam EM, Seynaeve C, Blom J, Brekelmans CT, Meijers-Heijboer H, van Asperen CJ, Cornelisse CJ, et al: Association between the CHEK2*1100delC germ line mutation and estrogen receptor status. Int J Gynecol Cancer. 16:552–555. 2006. View Article : Google Scholar : PubMed/NCBI
26	Cybulski C, Huzarski T, Byrski T, Gronwald J, Debniak T, Jakubowska A, Gorski B, Wokolorczyk D, Masojc B, Narod SA and Lubiński J: Estrogen receptor status in CHEK2-positive breast cancers: Implications for chemoprevention. Clin Genet. 75:72–78. 2009. View Article : Google Scholar : PubMed/NCBI
27	Kilpivaara O, Bartkova J, Eerola H, Syrjäkoski K, Vahteristo P, Lukas J, Blomqvist C, Holli K, Heikkilä P, Sauter G, et al: Correlation of CHEK2 protein expression and c.1100delC mutation status with tumor characteristics among unselected breast cancer patients. Int J Cancer. 113:575–580. 2005. View Article : Google Scholar : PubMed/NCBI
28	Broeks A, Braaf LM, Huseinovic A, Nooijen A, Urbanus J, Hogervorst FB, Schmidt MK, Klijn JG, Russell NS, Van Leeuwen FE and Van't Veer LJ: Identification of women with an increased risk of developing radiation-induced breast cancer: A case only study. Breast Cancer Res. 9:R262007. View Article : Google Scholar : PubMed/NCBI
29	Domagala D, Wokolorczyk D, Cybulski C, Huzarski T, Lubinski J and Domagala W: Different CHEK2 germline mutation are associated with distinct immunophenotyping molecular subtypes of breast cancer. Breast Cancer Res Treat. 132:937–945. 2011. View Article : Google Scholar : PubMed/NCBI
30	Huzarski T, Lener M, Domagala W, Gronwald J, Byrski T, Kurzawski G, Suchy J, Chosia M, Woyton J, Ucinski M, et al: The 3020insC allele of NOD2 predisposes to early-onset breast cancer. Breast Cancer Res Treat. 89:91–93. 2005. View Article : Google Scholar : PubMed/NCBI
31	Janiszewska H, Haus O, Lauda-Swieciak A, Bak A, Mierzwa T, Sir J and Laskowski R: The NOD2 3020insC mutation in women with breast cancer from the Bydgoszcz region in Poland. First results. Hered Cancer Clin Pract. 4:15–19. 2006. View Article : Google Scholar : PubMed/NCBI