High response rates to neoadjuvant platinum-based therapy in ovarian cancer patients carrying germ-line BRCA mutation

Gorodnova, Tatiana V.; Sokolenko, Anna P.; Ivantsov, Alexandr O.; Iyevleva, Aglaya G.; Suspitsin, Evgeny N.; Aleksakhina, Svetlana N.; Yanus, Grigoriy A.; Togo, Alexandr V.; Maximov, S.; Imyanitov, Evgeny N.

doi:10.1016/j.canlet.2015.08.028

Cited by 91 publications

(74 citation statements)

References 51 publications

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“…It has been shown that BRCA -mutant ovarian carcinoma, typically HGSC, may be associated with improved response to NACT,18 and these findings are consistent with the known association between BRCA mutation and hypersensitivity to platinum 19–21. However, it is thought that NACT may in fact promote platinum resistance in these patients, with data suggesting that NACT may provide a selection pressure towards BRCA -proficient cells 18.…”

Section: Clinical Aspects Of Neoadjuvant Chemotherapy (Nact)supporting

confidence: 62%

“…However, it is thought that NACT may in fact promote platinum resistance in these patients, with data suggesting that NACT may provide a selection pressure towards BRCA -proficient cells 18. NACT may therefore compromise the exquisite platinum sensitivity of BRCA -associated ovarian carcinoma by exposing a clonally diverse mass to the selection pressure of DNA-damaging agents 22 23.…”

Section: Clinical Aspects Of Neoadjuvant Chemotherapy (Nact)mentioning

confidence: 99%

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Neoadjuvant therapy in gynaecological malignancies: What pathologists need to know

McCarthy¹,

Rouzbahman²,

Thiryayi³

et al. 2019

J Clin Pathol

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In recent times, there has been a growing tendency to treat advanced gynaecological malignancies with neoadjuvant chemotherapy (NACT), with the goal of reducing tumour volume and enhancing operability resulting in optimal cytoreduction. This approach is used in particular for patients with advanced high-grade serous carcinoma of the ovary, fallopian tube or peritoneum. Pathology plays a crucial role in the management of these patients, both before and after NACT. Prior to initiation of NACT, a biopsy should be performed, usually of the omental cake, to confirm that a malignancy is present, to identify the site of origin of the tumour and to type and grade the tumour. Histopathologists must be aware of the resultant morphological effects of NACT when examining specimens following interval cytoreduction surgery. Tumour typing and grading, and even the identification of residual neoplasia, are particular challenges. Immunohistochemistry, when used judiciously, can be a useful adjunct in certain scenarios. A pathological assessment of the response to chemotherapy, and the pathological stage should be provided in the pathology report, as these may inform prognosis and subsequent management. We present a comprehensive overview of the relevant clinical and pathological aspects pertaining to NACT for gynaecological malignancies for the practicing surgical pathologist.

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Section: Clinical Aspects Of Neoadjuvant Chemotherapy (Nact)supporting

confidence: 62%

Section: Clinical Aspects Of Neoadjuvant Chemotherapy (Nact)mentioning

confidence: 99%

Neoadjuvant therapy in gynaecological malignancies: What pathologists need to know

McCarthy¹,

Rouzbahman²,

Thiryayi³

et al. 2019

J Clin Pathol

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“…That happens for unknown BRCA status patients as well, but with a smaller difference between groups (54 vs. 36%). Recent observations suggest a selection of tumour cell clones without somatic loss of heterozygosity (LOH) for the wild-type allele of BRCA genes, during neoadjuvant therapy [39].…”

Section: Discussionmentioning

confidence: 99%

Treatment Decisions and Survival in Ovarian Cancer

Nunes¹,

Mayer²,

FranciscaJorge³

et al. 2018

Cancer Management and Therapy

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Objective: to review the most recent data on the impact of the primary treatment and individual factors on ovarian cancer patient survival and to study it in a real world population. Methods/materials: retrospective analysis of 147 consecutive ovarian cancer patients treated with platin-based chemotherapy, either after primary debulking surgery (PDS) (n = 94, 64%) or as neoadjuvant (NACT) treatment (53, 36%). Results: NACT patients were older (64.3 vs. 58.2 years), with radiologically unresectable disease (74%) and/or comorbidities (26%). Fifty-five percent of pts. submitted to PDS were staged III/ IV. Serous carcinomas were equally distributed (PDS-57% vs. NACT-60%) but endometrioid (20 vs. 4%) and carcinomas not otherwise specified (6 vs. 30%) were more frequently diagnosed in the PDS and NACT group, respectively. Genetic diagnosis (24.4%): 11 BRCA1/2 and 1 RAD51C carriers identified. Residual disease after surgery was the only significant prognostic factor for both relapse (HR = 2267) and death (HR = 1847). Primary debulking surgery was associated with a significantly better PFS (HR = 0.541; p = 0.012) and with a trend to a better OS (HR = 0.714; p = 0.296). For pts. with III/IV disease OS was significantly superior in the PDS group. Conclusion: residual disease was the only significant prognostic factor. Primary surgery was associated with a significantly better PFS. The difference in OS was significant in stage III/IV patients. This reinforces the importance of maximal cytoreduction.

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“…More importantly, these correlations carry therapeutic relevance, as BRCA1/2-related breast and ovarian cancers demonstrate increased susceptibility to platinum-based chemotherapy and poly (ADP-ribose) polymerase (PARP) inhibition (13)(14)(15)(16)(17)(18). However, larger-scale studies soon recognized that BRCA1 and BRCA2 increase the risk of other cancer types as well.…”

Section: Min Yuen Teo 1 Eileen M O'reillymentioning

confidence: 99%

“…Clinically, considerable amount of evidence have been demonstrated in ovarian cancer (15,86,87) and breast cancer (13,14,88).…”

Section: Chemotherapy For Advanced Pancreatic Adenocarcinomamentioning

confidence: 99%

Is it time to split strategies to treat homologous recombinant deficiency in pancreas cancer?

Teo¹,

O'Reilly²

2016

J. Gastrointest. Oncol.

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Pancreatic cancer is a highly lethal malignancy which tends to present with late stage disease.To date, identification of oncogenic drivers and aberrations has not led to effective targeted therapy.Approximately 5-15% of pancreatic cancer has an inheritable component. In fact, pancreatic adenocarcinoma is now recognized as a BRCA1/2-related cancer. Germline BRCA1/2 mutations can be found in up to 3.6-7% of unselected pancreatic cancer patients although the rates are significantly higher amongst patients with Ashkenazi Jewish ancestry. Germline mutations of other components of DNA repair and homologous recombination have also been identified although at much lower frequency. Large sequencing efforts have further identified somatic mutations in these genes in a small subset of pancreatic cancers. Small series and case reports have suggested that pancreatic cancers harboring BRCA1/2 or other homologous repair gene mutations demonstrate enhanced response to platinum-based chemotherapy although this has not been prospectively validated. Clinical trials with poly (ADP-ribose) polymerase (PARP) inhibitors as monotherapy or in combination with chemotherapy in different clinical settings are currently on-going. A subtype of pancreatic adenocarcinoma as characterized by deficiency in homologous recombination exists although the optimal management strategy remains to be fully elucidated.

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High response rates to neoadjuvant platinum-based therapy in ovarian cancer patients carrying germ-line BRCA mutation

Cited by 91 publications

References 51 publications

Neoadjuvant therapy in gynaecological malignancies: What pathologists need to know

Neoadjuvant therapy in gynaecological malignancies: What pathologists need to know

Treatment Decisions and Survival in Ovarian Cancer

Is it time to split strategies to treat homologous recombinant deficiency in pancreas cancer?

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