Table 2.
Literature Review.
| Study | Setting/Design | Control Group | Number of Patients (n) | TNBC (n) | HER2-Positive (n) | Luminal (n) | BRCA1 | BRCA2 | BRCA 1 and 2 | Chemotherapy Regimen | sTILS Evaluation | pCR in BRCA-Carriers vs. Non-Carriers | Survival Analyses | Comments |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Byrski (2014) [26] {BCRT |
Neoadjuvant epidemiologic prospective cohort | No | 10 | 10 | 0 | 10 | 0 | 0 | 0 | Cis | No | 90% | No | 90% (9/10) in BRCA1-mutated BC patients achieved a pCR after NAC with cisplatin chemotherapy |
| Byrski (2015) [27] HCCP |
Neoadjuvant epidemiologic prospective cohort | No | 107 | 82 | 2 | NA | 107 | 0 | 0 | Cis | No | 61% | No | 61% (65/107) in BRCA1-mutated BC patients achieved pCR after NAC with cisplatin chemotherapy. In this study of BRCA1-mutation carriers, a pCR was also achieved in 56% of 16 patients with ER-positive BC. No survival analysis were provided in the current study. |
| Hanhnen (2017) [28] JAMA Oncology |
Neoadjuvant secondary analysis of the GeparSixto randomized clinical trial | Yes | 291 | 291 | 0 | 0 | 50 | 0 | P + Dox + Bev ± Cb | No | 66.7% vs. 36.4% | Yes | Patients with BRCA-mutation did not derive a pCR benefit from the addition of carboplatine (65.4% vs. 66.7%) compared to non-BRCA carriers (55% vs. 36.4%). No significant difference in overall prognosis observed in the BRCA-mutated subgroup. | |
| Sharma (2017) [39] CCR |
Neoadjuvant prospective, multicenter, non-randomized trial | Yes | 190 | 190 | 0 | 0 | 30 | 0 | Cb + D | No | 59% vs. 56% | No | No significative difference in pCR between BRCA-carriers and WT TNBC (59% and 56%, respectively (p = 0.83)). The Cb-D regimen was well tolerated and yielded high pCR rates in both BRCA associated and WT TNBC. These results are comparable to pCR of previous studies (who investigated pCR after NAC with addition of Cb to AT regimen in TNBC cohort). | |
| Poggio (2018) [20] Annals of Oncology |
Neoadjuvant meta-analysis of nine randomized controlled trials | No | 96 | 96 | 0 | 0 | 96 | 0 | P + Dox + Bev ± Cb P + AC ± Cb |
No | 54.3% | No | Among 96 BRCA-mutated patients included in 2 controlled trials, the addition of carboplatin was not associated with increased pCR rate (OR 1.17, 95% CI 0.51–2.67, p = 0.711). No survival analyses were available according to BRCA status. | |
| Telli (2019) [25] CCR |
Five randomized controlled trials | Yes | 161 | 161 | 0 | 0 | 34 | 0 | Cb + Gem + Iniparib; Cis; Cis + Bev; Cb + Eribulin; Cb + nab-P ± Vorinostat | Yes | No | No | pCR was achieved in 51 (31.7%) patients. In patients with TNBC treated with neoadjuvant platinum-based therapy, iTIL and sTIL densities were not significantly associated with BRCA1/2-mutated tumor status (p = 0.312 and p = 0.391). In multivariate analyses, sTIL density (OR 1.23, 95% CI 0.94–1.61, p = 0.139) was not associated with pCR, but was associated with RCB 0/I status (OR 1.62, 95% CI 1.20–2.28, p = 0.001). | |
| Sønderstrup (2019) [23] Acta Oncologica |
Epidemiologic prospective mulitcentric cohort (nationwide) | No | 411 | NA | 24 | NA | 243 | 168 | 0 | NA | Yes | No | Yes | High sTILs (defined as TILs > 60%) were observed in 36% in BRCA1- and 15% in BRCA2-mutated tumors (p < 0.0001). Significant association with survival (OS and DFS) was observed in BRCA1 subgroup. sTILs are an important prognostic factor in BRCA BC and increasing sTILs is associated with a better prognosis. |
| Byrski (2009) [17] JCO |
Neoadjuvant Epidemiologic epidemiologic retrospective cohort | No | 102 | NA | 6 | NA | 102 | 0 | 0 | CMF; AT; AC FAC or Cis | No | 23.5% | No | pCR was achieved in 23.5% of 102 patients with a BRCA1 mutation who received NAC. Especially, a complete pCR was observed in 8% (2/25) with AT- regimen (standard of care) compared to 83% (10/12) with cisplatin. |
| Chappuis (2002) [29] JMG |
Neoadjuvant Retrospective retrospective multicentric clinical trial | Yes | 38 | NA | NA | NA | 7 | 4 | 0 | FAC; AC; CEF AC + CMF AC + D |
No | 44% vs. 4% | No | pCR was achieved in 44% (4/11) of the BRCA-carriers and 4%(1/27) of the non-carriers (p = 0.009). No survival analysis were experienced in this study. |
| Arun (2011) [30] JCO |
Neoadjuvant Epidemiologic epidemiologic retrospective cohort | Yes | 317 | 77 | 60 | NA | 57 | 23 | 0 | A-single agent; AT or T-single-agent | No | 46% vs. 22% | Yes | pCR was achieved in 46% of BRCA1-carriers and 13% of BRCA2-carriers and 22% of BRCA non-carriers (<0.001). In the multivariate logistic model, BRCA1 status (OR = 1.96, p = 0.03) remained as independant significant predictors of a pCR. No significant difference in overall prognosis. |
| Wang (2014) [40] Annals of Oncology |
Neoadjuvant Epidemiologic retrospective cohort | Yes | 652 | 652 | 0 | 0 | 52 | NA | 0 | A-single agent; AT or T-single-agent | No | 53.8% vs. 29.7% | Yes | The pCR rate was 31.6% in the 652 patients who received NAC. BRCA1 carriers had a significantly higher pCR rate than non-carriers (BRCA1 carriers versus non-carriers, 53.8% versus 29.7%, p < 0.001). Among women treated with anthracycline with or without taxane regimens, the pCR rate was 57.1% for BRCA1 carriers, 29.0% for non-carriers (p < 0.001). The RFS was similar according to BRCA status. |
| Paluch-Shimon(2016) [31] BCRT |
Neoadjuvant epidemiologic retrospective cohort | Yes | 80 | 80 | 0 | 0 | 34 | 0 | 0 | AT | No | 68% vs. 37% | Yes | The BRCA1-carriers had pCR rate of 68% compared with 37% among non-carriers, p = 0.01. Yet this did not translate into superior survival for BRCA1 carriers compared with non-carriers. |
| Bignon (2017) [41] Breast |
Neoadjuvant epidemiologic retrospective cohort | No | 53 | 53 | 0 | 0 | 46 | 6 | 1 | A-single agent or AT | No | 66% | Yes | The pCR rate was 38.3% [95% CI, 26%–55%] among BRCA1 mutation carriers, and 66% among the 6 BRCA2 mutation carriers. 15 relapses and 6 s cancers were recorded during the follow-up period. 11 deaths occurred, all of which were in the non-pCR group. DFS (p < 0.01) and OS (p < 0.01) were significantly better in the pCR group than the non-pCR group. |
| Wunderle (2018) [18] BCRT |
Neoadjuvant Epidemiologic retrospective cohort | Yes | 355 | 138 | 58 | 159 | 43 | 16 | 0 | AT; Cb | No | 54.3% vs. 12.6% | Yes | pCR was observed in 54.3% of BRCA1/2 mutation carriers, but only in 12.6% of non-carriers. The adjusted odds ratio was 2.48 (95% CI 1.26–4.91) for BRCA1/2 carriers versus non-carriers. No difference in overall survival was observed. |
| Saether (2018) [32] HCCP |
Neoadjuvant Epidemiologic retrospective cohort | No | 12 | NA | NA | NA | 12 | 0 | 0 | Cis + Dox or Cb + D |
No | 83% | No | 11 patients received a combination of cisplatin and doxorubicin, and 1 patient received carboplatin and docetaxel. 83% (10/12) of the BRCA1-carriers achieved pCR. This results were comparable to existing results found in similar studies. No information about BC subtype among the study population and the toxicity of the chemotherapy was not evaluated. |
| Sella (2018) [19] Breast |
Neoadjuvant Epidemiologic retrospective cohort | Yes | 43 | 43 | 0 | 0 | 14 | 0 | 0 | AT ± Cb | No | 67% vs. 38% | No | pCR was achieved in 38% in BRCA WT compared to 67% in BRCA-associated TNBC (p = 0.232). No benefit from the addition of carboplatine in BRCA-carriers (64.3% vs. 67%) compared to non-BRCA carriers (44.8% vs. 38%) when compared to historic institutional rates with AT. |
| Solinas (2019) [24] Cancer Letters |
Epidemiologic retrospective cohort | Yes | 85 | 85 | 0 | 0 | 38 | 6 | 0 | NA | Yes | No | Yes | The BRCA-mutated tumors had a significantly higher incidence of TIL-positive levels compared to WT (44% and 41%, respectively p = 0.037). No significant difference between BRCA-mutated and WT groups neither in TIL subpopulation nor their location. No difference in I-DFS and OS after stratification on TIL infiltration levels. |
| Our study (2020) | Epidemiologic retrospective cohort | Yes | 267 | 110 | 67 | 90 | 31 | 14 | 1 | A-single agent; AT or T-single-agent | Yes | 45.7% vs 28% | Yes | Among the whole population, 84 tumors achieved a pCR (31.5%). After stratification by BC subtype, pCR rates were significantly higher in luminal BRCA-mutated BCs when compared with WT tumors (33.3% vs. 5.4%, p = 0.006).Pre and post-NAC str or IT TILs were not significantly different between BRCA-carriers and non-carriers in whole population. In the luminal BC, both str and IT post-NAC TIL levels were significantly higher in BRCA-mutated tumors when compared with WT tumors but was no longer significant after multivariate analysis. No difference in RFS or OS between BRCA-mutated and BRCA-WT patients. |
Abbreviations: CMF = cisplatine-methotrexate-fluorouracile; AT = doxorubicine-docetaxel; AC = doxorubicine-cyclophosphamide; FAC = fluorouracile-doxorubicin-cyclophophosphamide; CEF = cyclophosphamide-epirubicine-fluorouracile; A = anthracycline; Dox = doxorubicine; D = docetaxel; Cb = carboplatin; Cis = cisplatine; Bev = bevacizumab; Gem = gemcitabine; Nab-P = nabpaclitaxel; P = paclitaxel; T = taxane.