Table 1

Characteristics of the included RCTs

Study ID	Country	Center	Sample size at randomization	Clinical stage	Mean age (years)	BRCA (BRCA-1 or BRCA-2) mutation	Direct comparisons	Outcomes reported	Data extracted from subgroup analysis of RCT	Data in network meta-analysis (NMA)	Comparisons in NMA
Alba 2012	Spain	Multi	94	Non-metastatic (non-specific)	47 (median)	NR	EC-T vs. EC-TCb	pCR; AE (grade 3–4)	No	Yes	AT vs. ATPt
Ando 2014	Japan	Multi	75	II–IIIA	NR	NR	PCb-FEC vs. P-FEC	pCR	Yes	Yes	AT vs. ATPt
Bear 2012	USA (Puerto Rico), Canada, India	Multi	490	T1c-T3; N0-N2a; M0	NR	NR	T/TX/TG-AC + Bev vs. T/TX/TG-AC	pCR	Yes	No	NA
Chen 2016	China	Multi	102	IIB or III	NR	NR	TC vs. TAC	pCR	Yes	Yes	AT vs. TC
Earl 2015	UK	Multi	248	Early stage (non-specific)	NR	NR	T-FEC vs. T-FEC + Bev	pCR	Yes	Yes	AT vs. AT + Bev
Fasching 2019	Germany	Multi	77	Early stage (non-specific)	NR	NR	P-EC + Ola vs. PCb-EC	pCR	Yes	Yes	AT + Ola vs. ATPt
Gerber 2013	Germany	Multi	678	Untreated cT1c-T4d	48	18.3%BRCA1 mutation 15.1%BRCA2 mutation 3.2%	EC-T + Bev vs. EC-T	pCR	Yes	Yes	AT vs. AT + Bev
Geyer 2017	USA, Australia, Belgium, Canada, Czechia, France, Germany, Hungary, Italy, Korea, Netherlands, Russia, Spain, China (Taiwan), UK	Multi	634	Early stage (non-specific)	50 (median)	NR	PCb-AC + Veli vs. PCb-AC vs. P-AC	pCR; AE (grade 3–4)	No	Yes	AT vs. ATPt vs. ATPt + Veli
Gianni 2018	Australia, Germany, Italy, Russia, Singapore, Spain	Multi	219	T2N01; T3N0; T3N1; T4 any N; any T N2-3	NR	NR	P-AC/EC/FEC vs. nabP-AC/EC/FEC	pCR	Yes	No	NA
Gigolaeva 2019	Russia	NR	192	IIB–IIIA	47 (median)	BRCA1 mutation 12.0%	AC-P vs. AC-q3w PCb/EriCb	pCR	No	Yes	AT vs. ATPt
Gluz 2018	Germany	Multi	336	I–IV (IV-1.4%)	50	NR	q3w nabPG vs. q3w nabPCb	pCR; SAE	No	No	NA
Gonzalez-Angulo 2014	Germany	Single	62	IIA–IIIC	48	NR	P-FEC vs. P-FEC + Eve	pCR	No	Yes	AT vs. AT + Eve
Harbeck 2020	USA, Australia, Belgium, Brazil, Canada, Germany, Italy, Japan, Korea, Poland, Spain, China (Taiwan), UK	Multi	333	II–III	NR	NR	nabP-AC + Atezo vs. nabP-AC	pCR; AE (grade 3–5)	No	Yes	AT vs. AT + Atezo
Ishikawa 2016	Japan	Single	66	I–IIIC	53	NR	TC vs. FEC-T	pCR	Yes	Yes	AT vs. TC
Jovanovic 2017	USA	Multi	145	II or III	52	4.0%	PCis + Eve vs. PCis	pCR; AE (grade 3–5)	No	No	NA
Kummel 2017	Germany	Multi	131	cT2-T3	NR	NR	Caba vs. P	pCR	Yes	No	NA
Llombart-Cussac 2015	France, Germany, Spain	Multi	141	II–IIIA	NR	NR	P vs. P + weekly Ini vs. P + q2w Ini	pCR; treatment-related AE (grade 3–4)	No	No	NA
Loi 2019†	UK	Multi	60	Early stage (non-specific)	48.5 (median)	NR	nabP-AC + Pembro vs. nabPCb-AC + Pembro vs. PCb-AC + Pembro	pCR; SAE	No	No	NA
Loibl 2018	USA, Australia, Belgium, Canada, Czechia, France, Germany, Hungary, Italy, Korea, Netherlands, Russian, Spain, China (Taiwan), UK	Multi	634	II–III	50	Deleterious mutation 14.7%	PCb-AC + Veli vs. PCb-AC vs. P-AC	pCR; AE (grade 3–4)	No	Yes	AT vs. ATPt vs. ATPt + Veli
Loibl 2019	Germany	Multi	174	Early stage (non-specific)	49.5	NR	nabP-AC + Durva vs. nabP-AC	pCR; SAE	No	Yes	AT vs. AT + Durva
Martinez 2015	Mexico	NR	61	Locally advanced (non-specific)	47 (median)	NR	P-FAC vs. PA + Cis	pCR	No	Yes	AT vs. ATPt
Mayer 2019	USA	NR	140	I–III	NR	NR	Cis vs. P	pCR	No	No	NA
Nahleh 2016	USA (Puerto Rico), India	Multi	67	IIB–IIIC	NR	NR	nabP-AC + Bev vs. AC-nabP	pCR	Yes	Yes	AT vs. AT + Bev
Nanda 2020	USA	Multi	88	II–III	NR	NR	P-AC vs. P-AC + Pembro	pCR	Yes	Yes	AT vs. AT + Pembro
Rugo 2016	USA	Multi	60	II–III	NR	NR	P-AC vs. PCb-AC + Veli	pCR	Yes	Yes	AT vs. ATPt + Veli
Schmid 2020	USA, Australia, Brazil, Canada, Columbia, France, Germany, Ireland, Israel, Italy, Japan, Korea, Poland, Portugal, Russia, Singapore, Spain, Sweden, China (Taiwan), Turkey, UK	Multi	1174	II–III	NR	NR	PCb-AC/EC + Pembro vs. PCb-AC/EC	pCR; AE (grade ≥ 3)	No	Yes	ATPt vs. ATPt + Pembro
Schneeweiss 2019	Germany	Multi	403	Early stage (non-specific)	NR	NR	AC-q2wP vs. PA + Cb	pCR	Yes	Yes	AT vs. ATPt
Sharma 2019	USA	Multi	100	I–III	52 (median)	17.0%	PCb-AC vs. TCb	pCR; AE (grade 3–4)	No	Yes	ATPt vs. TCb
Sikov 2015	USA	Multi	454	II–III	NR	NR	P-AC vs. P-AC + Bev vs. PCb-AC vs. PCb-AC + Bev	pCR; SAE	No	Yes	AT vs. ATPt vs. AT + Bev vs. ATPt + Bev
Tung 2020	USA	Multi	83	I–III	NR	NR	Cis vs. AC	pCR	Yes	No	NA
Untch 2016	Germany	Multi	276	Early stage (non-specific)	NR	NR	nabP-EC vs. P-EC	pCR	Yes	No	NA
Von Minckwitz 2014	Germany	Multi	315	II–III	NR	15.9%	PACb + Bev vs. PA + Bev	pCR	No	No	NA
Wu 2018	China	Single	128	I–III	47 (median)	NR	ET vs. ET + Loba	pCR	No	No	NA
Zhang 2016	China	Single	91	II–III	47 (median)	NR	q3w PCb vs. q3w PE	pCR	No	No	NA
Zhang 2020	USA	Multi	93	Early stage (non-specific)	49 (median)	Deleterious mutation 12.2%	TCb vs. EC-T	pCR	No	Yes	AT vs. TCb

A, doxorubicin; SAE, serious adverse event; Atezo, atezolizumab; Bev, bevacizumab; BRCA mutation, mutations in 2 genes producing a hereditary breast-ovarian cancer syndrome; BRCA1, the first of these genes to be discovered; BRCA2, the second of these genes to be discovered; C, cyclophosphamide; Caba, cabazitaxel; Cb, carboplatin; Cis, cisplatin; Durva, durvalumab; E, epirubicin; Eve, everolimus; F, 5-fluorouracil; G, gemcitabine; Ini, iniparib; Loba, lobaplatin; nabP, albumin paclitaxel (weekly cycle if not specifically noted); NR, not reported; Ola, olaparib; P (weekly cycle if not specifically noted); Pt, platinum; pCR, pathologic complete response; Pembro, pembrolizumab; q2/3w: every 2/3 weeks; T, docetaxel; X, capecitabine. According to previous reports, guidelines, and clinical practice, a reasonable combination was made to maximize the inclusion of RCTs in NMA, which included the following: doxorubicin and epirubicin regarded as equal, cisplatin and carboplatin regarded as equal, TAC and AC-T regarded as equal, different sequential sequences regarded as equal (such as AC-P equal to P-AC, etc.). Citations for included RCTs are presented in Online Appendix 4. We excluded studies with interventions in only one study from this network meta-analysis (NMA). †Loi 2019 is a phase Ib study with 6 treatment arms exploring doses for chemotherapy combined with pembrolizumab, whose objective was not the primary focus in this NMA; each arm enrolled only 10 participants. We excluded this study from the outcome description and primary NMA analysis. In network meta-analysis, regimens including FECT, P-FAC, ACT, AC-nabP, and ACP were merged as anthracycline-taxane based (AT) regimens, and regimens including EC-TCb, PA + Cis/Cb, PCb-FEC, and PCb-AC were merged as anthracycline-taxane based + platinum (ATPt) regimens. (Sensitivity analyses were also performed on the basis of detailed regimens; details in Online Appendix 7: Supplementary Figures S7–S11 and Supplementary Tables S17–S22 and Online Appendix 8: Supplementary Figures S12–S15 and Supplementary Tables S23–S28).