Moiseyenko, Vladimir M
(Director, City Cancer Center, Saint Petersburg)
,
Chubenko, Vyacheslav A
(Department of Chemotherapy, City Cancer Center, Saint Petersburg)
,
Moiseyenko, Fedor V
(Department of Chemotherapy, City Cancer Center, Saint Petersburg)
,
Zagorskaya, Lyudmila A
(Department of Chemotherapy, City Cancer Center, Saint Petersburg)
,
Zaytseva, Yuliya A
(Department of Chemotherapy, City Cancer Center, Saint Petersburg)
,
Gesha, Nataliya E
(Department of Chemotherapy, City Cancer Center, Saint Petersburg)
,
Zykov, Evgeny N
(Laboratory of Nuclear Diagnostics, City Cancer Center, Saint Petersburg)
,
Ni, Valeriya I
(Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, Saint Petersburg)
,
Preobrazhenskaya, Elena V
(Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, Saint Petersburg)
,
Sokolenko, Anna P
(Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, Saint Petersburg)
,
Imyanitov, Evgeny N
(Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, Saint Petersburg)
This report describes an estrogen receptor-positive breast cancer patient, who relapsed at two and a half years after the completion of adjuvant chemotherapy while being on the aromatase inhibition. Based on the clinical evidence for potential sensitivity of the tumor to hormone ablation, everolimus...
This report describes an estrogen receptor-positive breast cancer patient, who relapsed at two and a half years after the completion of adjuvant chemotherapy while being on the aromatase inhibition. Based on the clinical evidence for potential sensitivity of the tumor to hormone ablation, everolimus was added to continuing exemestane treatment. Oral chemotherapy was administered at further disease progression, however, it lasted only for 10 days due to rapidly deteriorating condition of the patient. BRCA test was performed just before the failure of endocrine therapy and revealed a gross deletion within BRCA2 gene. Since the patient already developed contraindications to the standard chemotherapy, olaparib (300 mg twice a day) was given as a last hope option. The patient demonstrated a “Lazarus response”: the performance status and the results of the biochemical tests went back to the norm within first two weeks of treatment. Positron emission tomography-computed tomography (PET-CT) was performed at one month after the start of olaparib therapy, and revealed complete metabolic response for all multiple metastatic lesions located in the liver, bones, small pelvis, lungs, mediastinum, retroperitoneum, etc. Cytotoxic therapy and poly ADP-ribose polymerase (PARP) inhibitors are known to have virtually identical mechanisms of tumor escape from the treatment, which are confined to the restoration of BRCA proficiency within cancer cells. The pronounced tumor response to the treatment in this patient can be attributed to the lack of recent exposure to standard cytotoxic treatment as well as to the inability of tumors with gross BRCA rearrangements to restore BRCA function via secondary mutation. This observation calls for comprehensive evaluation of PARP inhibitors in chemonaive patients with hereditary cancer.
This report describes an estrogen receptor-positive breast cancer patient, who relapsed at two and a half years after the completion of adjuvant chemotherapy while being on the aromatase inhibition. Based on the clinical evidence for potential sensitivity of the tumor to hormone ablation, everolimus was added to continuing exemestane treatment. Oral chemotherapy was administered at further disease progression, however, it lasted only for 10 days due to rapidly deteriorating condition of the patient. BRCA test was performed just before the failure of endocrine therapy and revealed a gross deletion within BRCA2 gene. Since the patient already developed contraindications to the standard chemotherapy, olaparib (300 mg twice a day) was given as a last hope option. The patient demonstrated a “Lazarus response”: the performance status and the results of the biochemical tests went back to the norm within first two weeks of treatment. Positron emission tomography-computed tomography (PET-CT) was performed at one month after the start of olaparib therapy, and revealed complete metabolic response for all multiple metastatic lesions located in the liver, bones, small pelvis, lungs, mediastinum, retroperitoneum, etc. Cytotoxic therapy and poly ADP-ribose polymerase (PARP) inhibitors are known to have virtually identical mechanisms of tumor escape from the treatment, which are confined to the restoration of BRCA proficiency within cancer cells. The pronounced tumor response to the treatment in this patient can be attributed to the lack of recent exposure to standard cytotoxic treatment as well as to the inability of tumors with gross BRCA rearrangements to restore BRCA function via secondary mutation. This observation calls for comprehensive evaluation of PARP inhibitors in chemonaive patients with hereditary cancer.
4 The BRCA1-Δ11q alternative splice isoform bypasses germline mutations and promotes therapeutic resistance to PARP inhibition and cisplatin Cancer Res Wang Y Bernhardy AJ Cruz C 2778 2790 76 2016 27197267
5 Rapid selection of BRCA1-proficient tumor cells during neoadjuvant therapy for ovarian cancer in BRCA1 mutation carriers Cancer Lett Sokolenko AP Savonevich EL Ivantsov AO 127 132 397 2017 28377179
7 Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation J Clin Oncol Kaufman B Shapira-Frommer R Schmutzler RK 244 250 33 2015 25366685
9 Efficacy of capecitabine monotherapy as the first-line treatment of metastatic HER2-negative breast cancer Tumori Babacan T Efe O Hasirci AS 418 423 101 2015 25953439
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