Table 1.
Patient ID | Germline mutationa | Age at dx (years) | Stage at dx | Receptor status at dx | DNA-damaging tx received (line of MBC tx)c | Duration of response (months) | Best overall response | Reason for stopping tx | BRCA reversion status post-DNA- damaging tx | RAD51 foci status pre- DNA-damaging tx | RAD51 foci status post- DNA-damaging tx | Subsequent DNA-damaging tx exposure | Best response to subsequent DNA-damaging tx |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
292 | BRCA1 p.E23Vfs*17 | 44 | II | ER+/PR+/HER2− | Carboplatin (4th line) | 9 | SD | PD | No | UNK | UNK | None | NA |
303 | BRCA2 c.e9–1 (splice site, somatic) | 43 | III | ER+/PR+/HER2− | Cisplatin (5th line) | 15 | CR | PD | No | Absent | Absent | None | NA |
318 | BRCA2 p.E1493fs*10 | 51 | I | ER+/PR+/HER2− | Olaparib (5th line) | 11 | SD | PD | Yes, definite | Absent | Present | Carboplatin | Intrinsic resistance |
339 | BRCA2 p.L1908fs*2 | 30 | III | ER+/PR+/HER2− | Carboplatin (6th line) | 6 | UNK | PD | Yes, definite | Absent | Present | None | NA |
349 | BRCA1 p.S454* | 29 | I | ER+/PR+/HER2− | Olaparib (4th line) | 11 | PaR | PD | Yes, definite | Absent | Present | None | NA |
359 | BRCA1 p.T1677fs*2 | 53 | II | ER+/PR−/HER2− | Olaparib (2nd line) | 4 | SD | PD | No | Absent | Present | Carboplatin | Intrinsic resistance |
510 | BRCA2 p.S1720fs*7 | 58 | III | ER+/PR+/HER2− | Carboplatin ± veliparibb (6th line) | 9 | PaR | PD | Yes, putative | Absent | Present | None | NA |
565 | BRCA1 p.E23Vfs*16 | 42 | II | ER−/PR−/ HER2− | Veliparib (2nd line) | 20 | PaR | PD | No | Absent | Present | Carboplatin and olaparib (separate regimens) | Intrinsic resistance to both |
Anatomic stage is indicated. Best overall response was determined by RECIST (if patient on a clinical trial) or chart review by a breast medical oncologist (if patient not on a clinical trial). Intrinsic resistance is defined as progressive disease at first restaging or clinical progression before first restaging.
CR, complete response; dx, diagnosis; ER, estrogen receptor; fs, frameshift; MBC, metastatic breast cancer; NA, not applicable; ns, nonsense mutation; PD, progressive disease; PaR, partial response; PR, progesterone receptor; SD, stable disease; tx, treatment; UNK, unknown.
One patient (patient 303) had a somatic mutation in BRCA2.
This patient underwent blinded randomization to veliparib or placebo on a clinical trial.
Timelines indicating all treatments received by all patients, with to-scale durations, are shown in Figure 1, supplementary Figures S1 and S2, available at Annals of Oncology online, and Figure 3. Only DNA-damaging treatment associated with acquired resistance is indicated in the table (and with red arrows in treatment timelines). No patients received platinum or poly(adenosine diphosphate-ribose) polymerase inhibitors for non-metastatic disease.