open access

Vol 70, No 5 (2020)
Review article
Published online: 2020-10-05
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Genetics and Oncology (part 2.). Fundamentals of personalised medicine in the treatment of breast and ovarian cancer

Anna Doraczyńska-Kowalik, Gabriela Janus-Szymańska, Rafał Matkowski, Dagmara Michałowska, Maria M. Sąsiadek
DOI: 10.5603/NJO.2020.0040
·
Nowotwory. Journal of Oncology 2020;70(5):187-202.

open access

Vol 70, No 5 (2020)
Review article
Published online: 2020-10-05

Abstract

Individualisation of medical management based on prognostic and predictive markers (personalised medicine) allows customisation of prophylaxis and optimisation of treatment by increasing its efficiency and minimisation of adverse effects. In the case of breast cancer, therapy selection is still based on histopathology and immunohistochemical assessment including analysis of estrogen receptor (ER) expression, progesterone receptor (PgR) expression and over-expression or amplification of receptor tyrosine kinase erbB-2 gene (ERBB2 aka HER2). An additional role, facilitating decision on appli­cation or waiver of chemotherapy in early breast cancer, may be played by panels assessing gene expression within tDNA (tumour DNA, i.e. DNA isolated from tumour cells) and evaluation of concentration of uPA (urokinase-type plasminogen activator) and PAI-1 (plasminogen activator inhibitor type 1) in tumour cells. Growing hope surrounds the new, targeted therapies, including: inhibitors of CDK 4/6 (cyclin-dependant kinases 4 and 6), mTOR inhibitors (rapamycin’s mammalian target), inhibitors of poly(ADP-ribose)polymerase(PARP) or inhibitors of PI3K (phosphatidylinositol-4,5-bisphosphate 3-ki­nases). For ovarian cancer, treatment selection is based on assessment of the histopathologic type, malignancy degree, FIGO classification and platinum sensitivity of the tumour. However, the increasing use of PARP inhibitors and angiogenesis inhibitors is noteworthy. In the context of personalised medicine for both these cancers, an important element involves also individualisation of prophylactic and therapeutic recommendations in carriers of germline mutations associated with hereditary cancer syndromes.

Abstract

Individualisation of medical management based on prognostic and predictive markers (personalised medicine) allows customisation of prophylaxis and optimisation of treatment by increasing its efficiency and minimisation of adverse effects. In the case of breast cancer, therapy selection is still based on histopathology and immunohistochemical assessment including analysis of estrogen receptor (ER) expression, progesterone receptor (PgR) expression and over-expression or amplification of receptor tyrosine kinase erbB-2 gene (ERBB2 aka HER2). An additional role, facilitating decision on appli­cation or waiver of chemotherapy in early breast cancer, may be played by panels assessing gene expression within tDNA (tumour DNA, i.e. DNA isolated from tumour cells) and evaluation of concentration of uPA (urokinase-type plasminogen activator) and PAI-1 (plasminogen activator inhibitor type 1) in tumour cells. Growing hope surrounds the new, targeted therapies, including: inhibitors of CDK 4/6 (cyclin-dependant kinases 4 and 6), mTOR inhibitors (rapamycin’s mammalian target), inhibitors of poly(ADP-ribose)polymerase(PARP) or inhibitors of PI3K (phosphatidylinositol-4,5-bisphosphate 3-ki­nases). For ovarian cancer, treatment selection is based on assessment of the histopathologic type, malignancy degree, FIGO classification and platinum sensitivity of the tumour. However, the increasing use of PARP inhibitors and angiogenesis inhibitors is noteworthy. In the context of personalised medicine for both these cancers, an important element involves also individualisation of prophylactic and therapeutic recommendations in carriers of germline mutations associated with hereditary cancer syndromes.

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Keywords

personalised medicine; breast cancer; ovarian cancer; predictive tests; prognostic tests; germline mutations

About this article
Title

Genetics and Oncology (part 2.). Fundamentals of personalised medicine in the treatment of breast and ovarian cancer

Journal

Nowotwory. Journal of Oncology

Issue

Vol 70, No 5 (2020)

Pages

187-202

Published online

2020-10-05

DOI

10.5603/NJO.2020.0040

Bibliographic record

Nowotwory. Journal of Oncology 2020;70(5):187-202.

Keywords

personalised medicine
breast cancer
ovarian cancer
predictive tests
prognostic tests
germline mutations

Authors

Anna Doraczyńska-Kowalik
Gabriela Janus-Szymańska
Rafał Matkowski
Dagmara Michałowska
Maria M. Sąsiadek

References (23)
  1. Sąsiadek M, Łaczmańska I, Maciejczyk A, et al. Fundamentals of personalised medicine in genetic testing-based oncology. NOWOTWORY J Oncol. 2020; 70(4): 144–149.
  2. Cardoso F, Kyriakides S, Ohno S, et al. ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2019; 30(8): 1194–1220.
  3. Duffy MJ, Harbeck N, Nap M, et al. Clinical use of biomarkers in breast cancer: Updated guidelines from the European Group on Tumor Markers (EGTM). Eur J Cancer. 2017; 75: 284–298.
  4. Cardoso F, Senkus E, Costa A, et al. 4th ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4)†. Ann Oncol. 2018; 29(8): 1634–1657.
  5. André F, Ciruelos E, Rubovszky G, et al. SOLAR-1 Study Group. Alpelisib for -Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019; 380(20): 1929–1940.
  6. Low SK, Zembutsu H, Nakamura Y. Breast cancer: The translation of big genomic data to cancer precision medicine. Cancer Sci. 2018; 109(3): 497–506.
  7. Ross JS, Gay LM. Comprehensive genomic sequencing and the molecular profiles of clinically advanced breast cancer. Pathology. 2017; 49(2): 120–132.
  8. Paluch-Shimon S, Cardoso F, Sessa C, et al. ESMO Guidelines Committee. Prevention and screening in BRCA mutation carriers and other breast/ovarian hereditary cancer syndromes: ESMO Clinical Practice Guidelines for cancer prevention and screening. Ann Oncol. 2016; 27(suppl 5): v103–v110.
  9. Tung N, Lin NU, Kidd J, et al. Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer. J Clin Oncol. 2016; 34(13): 1460–1468.
  10. Kowalik A, Siołek M, Kopczyński J, et al. BRCA1 founder mutations and beyond in the Polish population: A single-institution BRCA1/2 next-generation sequencing study. PLoS One. 2018; 13(7): e0201086.
  11. Petrucelli N, Daly MB, Pal T. BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer. 1998 Sep 4 [Updated 2016 Dec 15]. In: Adam MP, Ardinger HH, Pagon RA, et al. ed. GeneReviews® [Internet]. University of Washington, Seattle 1993-2020.
  12. Li MM, Datto M, Duncavage EJ, et al. Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. J Mol Diagn. 2017; 19(1): 4–23.
  13. Antoniou AC, Casadei S, Heikkinen T, et al. Breast-cancer risk in families with mutations in PALB2. N Engl J Med. 2014; 371(6): 497–506.
  14. Schneider K, Zelley K, Nichols KE, et al. Li-Fraumeni Syndrome. 1999 Jan 19 [Updated 2019 Nov 21]. In: Adam MP, Ardinger HH, Pagon RA, et al. ed. GeneReviews® [Internet]. University of Washington, Seattle 1993-2020.
  15. Eng C. PTEN Hamartoma Tumor Syndrome. 2001 Nov 29 [Updated 2016 Jun 2]. In: Adam MP, Ardinger HH, Pagon RA, et al. ed. GeneReviews® [Internet]. University of Washington, Seattle 1993-2020.
  16. Thompson D, Duedal S, Kirner J, et al. Cancer risks and mortality in heterozygous ATM mutation carriers. J Natl Cancer Inst. 2005; 97(11): 813–822.
  17. Kaurah P, Huntsman DG. Hereditary Diffuse Gastric Cancer. 2002 Nov 4 [Updated 2018 Mar 22]. In: Adam MP, Ardinger HH, Pagon RA, et al. ed. GeneReviews® [Internet]. University of Washington, Seattle 1993-2020.
  18. Stjepanovic N, Moreira L, Carneiro F, et al. ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Hereditary gastrointestinal cancers: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2019; 30(10): 1558–1571.
  19. McGarrity TJ, Amos CI, Baker MJ. Peutz-Jeghers Syndrome. 2001 Feb 23 [Updated 2016 Jul 14]. In: Adam MP, Ardinger HH, Pagon RA, et al. ed. GeneReviews® [Internet]. University of Washington, Seattle 1993-2020.
  20. Ledermann JA, Raja FA, Fotopoulou C, et al. ESMO Guidelines Working Group. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013; 24 Suppl 6: vi24–vi32.
  21. Walsh T, Casadei S, Lee MK, et al. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci U S A. 2011; 108(44): 18032–18037.
  22. Kohlmann W, Gruber SB. Lynch Syndrome. 2004 Feb 5 [Updated 2018 Apr 12]. In: Adam MP, Ardinger HH, Pagon RA, et al. ed. GeneReviews® [Internet]. University of Washington, Seattle 1993-2020.
  23. Suszynska M, Ratajska M, Kozlowski P. BRIP1, RAD51C, and RAD51D mutations are associated with high susceptibility to ovarian cancer: mutation prevalence and precise risk estimates based on a pooled analysis of ~30,000 cases. J Ovarian Res. 2020; 13(1): 50.

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