Cytotoxic and targeted therapy for hereditary cancers

Iyevleva, Aglaya G.; Imyanitov, Evgeny N.

doi:10.1186/s13053-016-0057-2

Cited by 49 publications

(58 citation statements)

References 157 publications

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“…3 Primary debulking surgery followed by adjuvant platinumbased therapy is a preferable treatment strategy for women, in whom both the disease spread and the pattern of comorbidities are compatible with complete surgical removal of the tumor masses. In many instances, even extensive surgery cannot result in optimal debulking and/or the risk of serious perioperative complications is unacceptably high.…”

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confidence: 99%

Atl

Gorodnova

Kotiv

Ivantsov

et al. 2018

Int J Gynecol Cancer

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ObjectivesCisplatin and mitomycin C exert high activity towards BRCA1-deficient cells. This study aimed to evaluate the efficacy of a combination of these drugs in hereditary BRCA1-associated ovarian cancer (OC).MethodsTwelve OC patients, who could not be treated by primary debulking surgery owing to extensive tumor spread, were given neoadjuvant cisplatin (100 mg/m2) and mitomycin C (10 mg/m2) every 4 weeks for 3 (n = 9), 2 (n = 2), or 4 (n = 1) cycles.ResultsThe decrease of tumor burden and complete surgical cytoreduction were achieved in all patients. Pathologic complete response, defined as the absence of tumor cells in surgically removed tissues, was observed in 2 (17%) of 12 cases. Retrospective analysis of 62 OC in BRCA1 mutation carriers subjected to conventional neoadjuvant chemotherapy schemes revealed 36 objective tumor responses (58%) and 37 instances (60%) of complete cytoreductive surgery; however, none of these patients demonstrated pathologic complete response.ConclusionsThe combination of cisplatin plus mitomycin C showed promising results in BRCA1-driven OC and therefore deserves further clinical evaluation.

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confidence: 99%

Atl

Gorodnova

Kotiv

Ivantsov

et al. 2018

Int J Gynecol Cancer

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“…BRCA1 is essential for taxane-driven apoptosis. There is laboratory and clinical evidence suggesting inferiority of taxane-based drug schemes compared with taxane-free drug combinations in BRCA1 -associated tumors 6. This study did not have sufficient power to compare the efficacy of therapies with and without taxanes in BRCA1 mutation carriers.…”

Section: Discussionmentioning

confidence: 87%

BRCA1-associated and sporadic ovarian carcinomas: outcomes of primary cytoreductive surgery or neoadjuvant chemotherapy

Gorodnova

Sokolenko

et al. 2019

Int J Gynecol Cancer

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ObjectiveTumors arising in BRCA1/2 mutation carriers are characterized by increased platinum sensitivity; however, it is unknown whether this feature should be considered while choosing between primary surgical versus systemic treatment. This study aimed to compare outcomes of ovarian cancer patients undergoing either primary surgery or interval cytoreduction based on BRCA1/2 status.MethodsThe study included consecutive ovarian cancer patients, who were treated at the N.N. Petrov Institute of Oncology (St Petersburg, Russia) from 2000 to 2013 and who underwent complete or optimal cytoreductive surgery. A comparison of disease outcomes was performed for the total group of ovarian cancer patients as well as for 69 BRCA1-mutated and 151 sporadic high-grade serous advanced-stage ovarian carcinomas. Frequency comparisons were performed by Chi-square test or Fisher exact test. Disease-free interval and overall survival were analyzed by Mann-Whitney U-test and Kaplan-Meier method. Hazard ratios were calculated by Cox regression analysis.ResultsThe analysis included 283 consecutive patients who underwent optimal cytoreduction (size of residual tumor <1 cm (n=156)) or complete tumor excision (n=127) on primary surgery (n=168) or after neoadjuvant chemotherapy (n=115). 84 patients carried germline mutation in BRCA1 (n=77) or BRCA2 (n=7) genes, while 199 ovarian cancer patients were classified as sporadic. High-grade serous ovarian cancer patients treated with neoadjuvant chemotherapy had a lower disease-free interval compared with those undergoing primary surgery followed by adjuvant therapy (7.8 vs 14.2 months, p<0.001). This difference was attributed mainly to sporadic cases (5.1 vs 12.2 months, p<0.001), while BRCA1-associated cancers had a similar disease-free interval regardless of the sequence of treatments (12.5 vs 15.8 months, p=0.53). When treated with neoadjuvant chemotherapy, BRCA1-mutated patients had improved overall survival as compared with sporadic cases (45.7 vs 25.3 months, p=0.007), while patients subjected to primary surgery showed similar overall survival irrespective of BRCA1 status (54.6 vs 53.9 months, p=0.56). A total of 29/61 (48%) BRCA1/2-associated patients relapsed as a single local tumor; this was lower in sporadic cancer patients (38/134 (28%); p=0.01).ConclusionIn BRCA1 mutation carriers, the oncologic outcomes are similar when comparing primary surgery versus neoadjuvant chemotherapy. In addition, BRCA1-mutation carriers often have a single site of disease when diagnosed with recurrent ovarian cancer.

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“…Эти опухоли ха-рактеризуются выраженной геномной нестабильностью и достаточно агрессивным течением. BRCA2-ассоции-рованные карциномы демонстрируют избирательную чувствительность к производным платины и ингибито-рам фермента PARP [3].…”

Section: опухоли женской репродуктивной системы Tumors Of Female Reprunclassified

Cyclin-Dependent Kinase Inhibitor, Palbociclib – A New Drug for the Treatment of Metastatic Breast Cancer

Имянитов¹,

Семиглазова²

2017

Tumors of female reproductive system

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ОПУХОЛИ ЖЕНСКОЙ РЕПРОДУКТИВНОЙ СИСТЕМЫ TUMORS OF FEMALE REPRODUCTIVE SYSTEM Russia; 2 Litovskaya St., Saint Petersburg 194100, Russia The sequential use of several lines of endocrine therapy is considered the standard for the treatment of metastatic breast cancer, expressing estrogen or progesterone receptors. studies showed that the combination of the inhibitor of CDK4/6, palbociclib, with endocrine therapy significantly increases the time to progression compared to the use of monotherapy with antagonists of the estrogen signaling cascade. Key words: metastatic ER-positive breast cancer, factors of poor prognosis, resistance, hormonal therapy, palbociclibВведение Рак молочной железы (РМЖ) обычно подразделя-ют на биологические подтипы в зависимости от экс-прессии рецепторов эстрогенов (estrogen receptors, ER), прогестерона (progesterone receptors, PR) и HER2. При этом принято считать, что ER / PR-положительные опухоли характеризуются относительно благополуч-ным прогнозом. Следует понимать, что само понятие о благоприятном течении онкологического заболева-ния является достаточно условным. Если мы говорим об опухолях молочной железы, рост которых зависит от воздействия эстрогенов, то в условиях своей естест-венной прогрессии они имеют тенденцию поражать лимфатические узлы и костную ткань, но при этом от-носительно редко метастазировать в печень, легкие, мозг. Таким образом, даже при отсутствии или неэф-фективности терапии женщины с эстроген-зависимым РМЖ живут в целом несколько дольше по сравнению с больными трижды негативным или HER2-положи-тельным РМЖ. Если же пациентка получает после опе-рации специфическую адъювантную терапию (напри-мер, тамоксифен), риск рецидива заметно снижается. Но при всем этом утверждение о благоприятном тече-нии РМЖ, экспрессирующего ER, имеет колоссальные ограничения.Во-первых, далеко не все карциномы, экспресси-рующие ER, действительно отвечают на терапию та-моксифеном, ингибиторами ароматазы или фулве-странтом. У значительного числа пациенток ER действительно присутствуют в опухолевых клетках, но ответа на специфическую терапию не происходит -либо за счет того, что прогрессия опухолевого клона 35М а м м о л о г и я / M a m m o l o g y 4 ' 2 0 1 7 Том 13 / Vol. 13 ОПУХОЛИ ЖЕНСКОЙ РЕПРОДУКТИВНОЙ СИСТЕМЫ TUMORS OF FEMALE REPRODUCTIVE SYSTEMо н стат и de facto не зависит от активности сигнального каскада эстрогенов, либо вследствие неэффективности инак-тивации данного рецептора.Во-вторых, даже если применение гормональной терапии (ГТ) имеет определенный эффект, его дли-тельность ограничена во времени, а сам ответ опухоли на такое лечение, как правило, является неполным. Более того, ER-положительные клетки РМЖ, обладая невысоким пролиферативным потенциалом и низким уровнем геномной нестабильности, отличаются лишь умеренной чувствительностью к химиотерапии (ХТ). Получается, что диапазон возможных действий врача в отношении ER-положительного РМЖ достаточно ограничен, так как после приобретения опухолью ре-зистентности к ГТ остается не так много вариантов эффективного лечения.В настояще...

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Cytotoxic and targeted therapy for hereditary cancers

Cited by 49 publications

References 157 publications

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BRCA1-associated and sporadic ovarian carcinomas: outcomes of primary cytoreductive surgery or neoadjuvant chemotherapy

Cyclin-Dependent Kinase Inhibitor, Palbociclib – A New Drug for the Treatment of Metastatic Breast Cancer

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