links.lww.com/COON/A27

(1)

Supplementary Table 1. Risk factors associated to MaBC.

Increasing Age

Genetic factors Well-established Family history BRCA2 >> BRCA1

Possible PALB2

Androgen Receptor CYP17

CHEK2 Conditions

associated with an abnormal estrogen- to-androgen ratio

Klinefelter syndrome

Exogenous estrogen or testosterone use Obesity

Marijuana use Orchitis/epididymitis Thyroid disfunction Finasteride Lifestyle Lack of exercise

Exposures Well-established Radiation

Possible Electromagnetic fields Heat

Volatile organic compounds (eg, tetrachloroethylene, perchloroethylene, trichloroethylene, dichloroethylene, and benzene) or chemicals Miscellaneous

possible risk factors Birth order (possible higher risk in first borns) Bone fracture after age 45

(2)

Trial Number Test Lymph node status Number of patients enrolled

N. of men enrolled

(%)

Primary Outcome Enrollment period NCT00310180

TAILORx Oncotype DX Negative 10,253 0 (0%)* iDFS 2006 – 2010

NCT00433589

MINDACT MammaPrint Negative or positive

(max 3) 6,693 0 (0%)* DMFS

DFS 2007 – 2011

NCT01049425

WSG PlanB Oncotype DX Negative or positive 3,198 0 (0%)* DFS 2009 – 2011

NCT01272037

RxPONDER Oncotype DX Positive (1-3) 10,000 0 (0%)* DFS 2011 – 2015

ISRCTN42400492 OPTIMA

Prosigna (PAM50)

Positive (max 9) 4,500 (estimated

main trial)

ongoing, open to men

iDFS Cost-effectiveness

of test-directed therapy

2017 – ongoing

Supplementary Table 2. Multi-parameter gene expression assays trials for EBC. *male gender was an

exclusion criterion for this trial. Abbreviations: DFS: Disease-Free Survival; iDFS: invasive Disease-Free

Survival; DMFS: Distant Metastasis-Free Survival; RS: Recurrence Score.

(3)

Trial Number Experimental Treatment

Arm

Control Arm/Active Comparator

Phase Setting Number of patients enrolled

N. of men

enrolled (%) Primary

Outcome Enrollment period

(4)

NSABP B-05 Adj L- phenylalanine mustard

Adj Placebo 3 Adjuvant

N+ 379 0 (0%)* DFS 1972 - 1974

NSABP B-09 L-phenylalanine mustard + 5-FU + Tamoxifen

L-

phenylalanine mustard + 5-FU

3 Adjuvant

N+ 1891 0 (0%)* DFS 1977 - 1981

NSABP B13 Methotrexate + Fluorouracil followed by Leucovorin

Observation 3 Adjuvant

TNBC N0

760 0 (0%)* DFS 1981 - 1988

NSABP B-14 Tamoxifen Placebo 3 Adjuvant

HR+/HER2- N0

2,892 0 (0%)* DFS

OS 1982 - 1988 NSABP B-15 Arm1: AC x 4

Arm 2: AC x 4 ->

CMF x 3 Arm 3: CMF x 6

n.a. 3 Adjuvant

N+

Tamoxifen non- responsive

2,194 0 (0%)* DFS

DDFS OS

1984 - 1988

NSABP B-20 Arm1: CMF + Tamoxifen Arm 2:

Methotrexate + 5-FU followed by Tamoxifen

Tamoxifen 3 Adjuvant

HR+/HER2- 2,306 0 (0%)* DFS

OS 1988 - 1993

NSABP B-22 Arm 1: AC (intensification of C)

Arm 2: AC (intensification + increased total dose of C)

AC “standard

dose” 3 Adjuvant

N+ 2,305 0 (0%)* DFS 1989 - 1991

Trial MA5 FEC CMF 3 Adjuvant

N+ 710 0 (0%)* RFS

OS 1989 - 1993

INT 0101 (E5188) Arm 1: CAF-Z

Arm 2: CAF-ZT CAF 3 Adjuvant

HR+/HER2- N+

1,503 0 (0%)* DFS

OS 1989 - 1994

NCT00929591

SWOG-8814 Arm 1: CAF followed by Tamoxifen for five years.

Arm 2: CAF with concurrent Tamoxifen for five years

Tamoxifen for

five years 3 Adjuvant 1,558 0 (0%)* DFS

OS Toxicity

1989 - 1995

NCT00309491

ABCSG Trial 6 Tamoxifen +

Aminoglut. Tamoxifen 3 Adjuvant

HR+/HER2- 2,020 0 (0%)* OS 1990 - 1999

NCT00003678

aTTom Tamoxifen for 10

yrs Tamoxifen for

5 yrs 3 Adjuvant

HR+/HER2- 6,953 0 (0%)* OS 1991 - 2005

GABG-IV D-93 Tamoxifen after

risk-adapted CT Observation after risk- adapted CT

3 Adjuvant

TNBC 829 0 (0%)* DFS

OS Toxicity

1993 - 2000

GABG-IV A-93 Goserelin CMF 3 Adjuvant

HR+/HER2- N0

771 0 (0%)* EFS 1993 - 2001

NSABP B-28 AC (4 cycles) -->

Paclitaxel (4 cycles)

AC alone

(4 cycles) 3 Adjuvant

N+ 3,060 0 (0%)* DFS

OS 1995 - 1998

NCT00300508

ABCSG Trial 6a Anastrazole after Tamoxifen +/- AI (tot 5 yrs)

Observation after Tamoxifen +/- AI (tot 5 yrs)

3 Adjuvant

HR+/HER2- 856 0 (0%)* RFS

OS 1996 - 1999

NCT00849030

ATAC n.a. Arm 1:

Tamoxifen + Anastrozole Arm 2:

Tamoxifen + Placebo Arm 2:

Anastrozole + Placebo

3 Adjuvant

HR+/HER2- 9,358 0 (0%)* DFS

Safety and AEs

1996 - 2000

NCT00287534 ARNO 95

Anastrazole after Tamoxifen (tot 5 yrs)

Tamoxifen (tot 5 yrs)

2 Adjuvant

HR+/HER2-

1,059 0 (0%)* DFS 1996 – 2002

NCT00291759

ABCSG 8 Anastrazole after Tamoxifen (tot 5 yrs)

Tamoxifen

(tot 5 yrs) 3 Adjuvant

HR+/HER2- 3,901 0 (0%)* EFS

OS 1996 – 2004

NCT00003016 ATLAS

Tamoxifen for 10 yrs

Tamoxifen for 5 yrs

3 Adjuvant

HR+/HER2-

12,894 0 (0%) OS 1996 – 2005

NCT00003088

CALGB-9741 Arm 1: A -> T ->

C (21 days) Arm 2: AC -> T (14 days) Arm 3: A -> T ->

C (14 days)

n.a 3 Adjuvant

N+ 2,005 0 (0%)* DFS 1997 - 1999

(5)

Arm 4: AC -> T (21 days) US Oncology

Research Trial 9735

TC (4 cycles) AC (4 cycles) 3 Adjuvant

N+ 1,016 0 (0%)* DFS

OS 1997 - 2000

NCT00286117

ITA Anastrazole after Tamoxifen (tot 5 yrs)

Tamoxifen

HR+/HER2- 426 0 (0%)* DFS 1998 - 2002

NCT00003140

MA.17 Letrozole after Tamoxifen (tot 5 yrs)

Placebo after Tamoxifen (tot 5 yrs)

3 Adjuvant

HR+/HER2- 5,187 0 (0%)* DFS 1998 - 2003

NCT00038467

IES Exemestane

after Tamoxifen (tot 5 yrs)

Tamoxifen

HR+/HER2- 4,742 0 (0%)* DFS 1998 - 2003

NCT00004205

BIG 1-98 Arm 1:

Tamoxifen for 5 yrs

Arm 2: Letrozole for 5 yrs Arm 3:

Tamoxifen for 2 yrs followed by Letrozole for 3 yrs

Arm 4: Letrozole for 2 yrs followed by Tamoxifen for 3 yrs

n.a. 3 Adjuvant

HR+/HER2- 8,010 0 (0%)* DFS 1998 - 2003

NCT00004125

ECOG E1199 Paclitaxel or Docetaxel after AC (different schedules)

n.a. 3 Adjuvant 4,950 0 (0%)* DFS 1999 - 2002

NSABP B30 Arm 1:

ACDocetaxel Arm 2: A + Docetaxel Arm 3: AC + Docetaxel

n.a. 3 Adjuvant

N+ 5,351 0 (0%)* DFS 1999 - 2004

ISRCTN76560285

FinHER Arm 1 HER2+:

Docetaxel/FEC/

Trastuzumab Arm 2 HER2+:

Vinorelbine/FEC /Trastuzumab Arm 1 HER2-:

Docetaxel/FEC/

Arm 2 HER2-:

Vinorelbine/FEC

Arm 1 HER2+:

Docetaxel/

FEC Arm 2 HER2+:

Vinorelbine/

FEC

3 Adjuvant

HER2+

N+ or high- risk

1,010 0 (0%)* DFS 2000 - 2003

NCT00004067

NSABP B31 AC followed by Paclitaxel + Trastuzumab

AC followed

by Paclitaxel 3 Adjuvant HER2+

N+

2,130 0 (0%)* DFS

Cardiotoxicity 2000 - 2005 NCT00005970

NCCTG N9831 Arm1 & 2: AC followed by Paclitaxel + Trastuzumab +/- Tamoxifene/AI (different schedules)

AC followed by Paclitaxel +/-

Tamoxifene/AI

3 Adjuvant

HER2+

N+ or high- risk N0

3,436 0 (0%)* DFS 2000 - 2005

ISRCTN79718493

TACT FEC x 4 -->

Docetaxel x 4 FEC x 8 or epirubicin x 4 --> CMF x 4

3 Adjuvant

N+ or high- risk N0

4,162 0 (0%)* DFS 2001 - 2003

NCT00054587

PACS04 Epirubicin -Docetaxel x 6 -->Trastuzumab

FEC x 6 -->

Trastuzumab 3 Adjuvant

HER2+

N+

3,010 0 (0%)* PFS 2001 - 2004

NCT00021255

BCIRG 006 Arm 1: AC followed by Docetaxel + Trastuzumab Arm 2:

Carboplatin + Docetaxel + Trastuzumab

AC followed

by Docetaxel 3 Adjuvant

HER2+

N+ or high- risk N0

3,222 0 (0%)* DFS 2001 - 2004

NCT00045032

HERA Arm 1: Adj Trastuzumab for 1 yr

Arm 2: Adj Trastuzumab for 1 yrs

Observation 3 Adjuvant

HER2+ 5,081 0 (0%)* DFS 2001 - 2005

NCT00279448 NCT00032136 NCT00036270

TEAM

Exemestane for

5 yrs Tamoxifen for

2-3 years, followed by Exemestane for a total 5 yrs

3 Adjuvant 9,779 0 (0%)* DFS 2001 - 2006

NCT00024102

CALGB 49907 Capecitabine Physician

choice 3 Adjuvant

≥ 65 yrs 633 0 (0%)* DFS 2002 - 2006

(6)

-old NCT00070564

SWOG S0221

Doxorubicin+

cyclophosphami de followed by paclitaxel (different schedules)

Doxorubicin + cyclophospha mide followed by paclitaxel (different schedules)

3 Adjuvant

EBC, LABC

3,294 23 (0.7%) DFS

OS

2003 - 2010

NCT00066703

TEXT Exemestane + OFS (GnRH analogue) for 5 yrs

Tamoxifen + OFS (GnRH analogue) for 5 yrs

3 Adjuvant

HR+/HER2- 2,672 0 (0%)* DFS 2003 – 2011

NCT00066690

SOFT Arm 1:

Tamoxifen + OFS (GnRH analogue) for 5 yrs

Arm 2:

Exemestane + OFS (GnRH analogue) for 5 yrs

Tamoxifen for

5 yrs 3 Adjuvant

HR+/HER2- 3,066 0 (0%)* DFS 2003 – 2011

NSABP B-36 AC x 4 FEC x 6 3 Adjuvant

N0 2,722 0 (0%)* DFS 2004 - 2008

NCT00754845

MA.17R Letrozole for 5 yrs after Adj Tamoxifen

Placebo for 5 yrs

after Adj Tamoxifen

3 Adjuvant

HR+/HER2- 1,918 0 (0%)* DFS 2004 - 2009

NCT00301457

DATA Anastrozole for

6 yrs Anastrozole

for 3 yrs 3 Adjuvant

HR+/HER2- 1,912 0 (0%)* DFS 2006 – 2009

NCT00381901

PHARE Adj

Trastuzumab for 6 months

Adj Trastuzumab for 12 months

3 Adjuvant

HER2+ 3,384 0 (0%)* DFS 2006 - 2010

NCT00382070

NSABP-B42 Letrozole for up

to 5 yrs. Placebo for up

to 5 yrs 3 Adjuvant

HR+/HER2- 3,966 0 (0%)* DFS 2006 – 2010

NCT00528567

BEATRICE Bevacizumab +

CT CT 3 Adjuvant

TNBC 2,591 0 (0%) iDFS 2007 – 2010

NCT00542451

APT Adj Paclitaxel +

Trastuzumab n.a. 2 Adjuvant

HER2+

N0

420 1 (0.2%) DFS 2007 – 2010

NCT00490139 BIG 2-06/N063D

ALTTO

Arm 1. Lapatinib Arm 2. Lapatinib followed by Trastuzumab Arm 3. Lapatinib +Trastuzumab

HER2+

EBC and LABC

8,382 9 (0.1%) DFS 2007 – 2011

Eudra-CT 2006- 003958-16

IDEAL

Letrozole for 5 years after 5-yrs adj ET

Letrozole for 2.5 years after 5-yrs adj ET

3 Adjuvant

HR+/HER2- 1,824 0 (0%) DFS 2007 – 2011

UMIN000000843

CREATE-X Capecitabine Observation 3 Adjuvant

TNBC residual invasive disease after neoadj

CT

910 0 (0%)* DFS 2007 – 2012

NCT00541086

FATA-GIM3 Arm 1:

Anastrozole for 5 yrs Arm 2:

Exemestane for 5 yrs

Arm 3: Letrozole for 5 yrs

Arm 4:

Tamoxifen for 2 yrs followed by

anastrozole for 3 yrs.

Arm 5:

Tamoxifen for 2 yrs followed by

exemestane for 3 yrs.

Arm 6:

Tamoxifen for 2 yrs followed by Letrozole for 3 yrs.

3 Adjuvant

HR+/HER2- 3,697 0 (0%)* DFS 2007 - 2012

NCT01358877

APHINITY Pertuzumab + Trastuzumab + CT

Placebo + Trastuzumab + CT

3 Adjuvant

HER2+ 4,805 11 (0.2%) iDFS 2011 – 2013

NCT01772472

KATHERINE T-DM1 Trastuzumab 3 Adjuvant

HER2+

with residual disease

1,486 5 (0.3%) iDFS 2013 – 2015

NCT02040857 Palbociclib, + ET n.a. 2 Adjuvant

HR+

EBC, LABC

162 5 (3%) Treatment

Discontinua- tion Rate

2014 – 2015

NCT02132949 Cohort A – neoadj: dose dense AC, Paclitaxel,

n.a. 2 Neoadj/

Adjuvant HER2+

EBC,

400 1 (0.3%) Cardiotoxicity 2014 – 2016

(7)

Pertuzumab, Trastuzumab;

Adj:

Cohort B - neoadj: FEC, Docetaxel, Pertuzumab, Trastuzumab;

Adj:

LABC, IBC

NCT02032823 NSABP B55

OlympiA

Olaparib after

Adj treatment Placebo after

Adj treatment 3 Adjuvant gBRCA1-2 HR+/HER2-

or TNBC

1,836 n.a. iDFS 2014 – 2019

NCT02586025 Trastuzumab, Pertuzumab, Docetaxel

Trastuzumab, Placebo, Docetaxel

3 Neoadj/

Adjuvant HER2+

EBC and LABC

329 0 (0%) tpCR 2016 – 2017

Supplementary Table 3. Clinical trials mentioned for the adjuvant setting in the NCCN Clinical Practice Guidelines in Oncology – version 2.2020. Gender-related inclusion criteria and number of men enrolled are reported. *male gender was an exclusion criterion for this trial. Abbreviations: adj: adjuvant; neoadj:

neoadjuvant; yrs: years; yr: year; ET: endocrine therapy; CMF: cyclophosphamide, methotrexate, fluorouracil, and tamoxifen; N: Lymph Node status; mut: mutated; HR+: Hormone Receptor-positive; HER2-:

HER2-negative; DFS: Disease-Free Survival; GnRH: Gonadotropin-Releasing Hormone; OFS: Ovarian Function Suppression; F-up: Follow-up; A: Adriamycin; C: Cyclophosphamide; AI: Aromatase Inhibitor; AE:

Adverse Event; CAF: cyclophosphamide + doxorubicin + fluorouracil; CAF-Z: CAF followed by 5 years of monthly goserelin; CAF-ZT: CAF followed by 5 years of monthly goserelin and daily tamoxifen; EFS: Event- free survival; tot: total; Aminoglut: Aminoglutethimide; DFS: Disease-Free Survival; iDFS: invasive Disease- Free Survival; OS: Overall Survival; EFS: Event-Free Survival; T: Paclitaxel; TC: docetaxel / cyclophosphamide; AC: doxorubicin/cyclophosphamide; FEC: 5-FU, Epirubicin, Cyclophosphamide.

Trial Number

Name Experimental

Treatment Arm

Control

Arm Phas

e Setting Primary Outcome Status Actual/

Estimated Primary Completion

(8)

Date NCT04247633

HIPEx Palbociclib + ET Palbociclib 2 Adjuvant

High Risk ER+ HER2-

EFS Not yet

recruiting February, 2023

NCT02927249 ET + Aspirin ET + Placebo 3 Adjuvant

HR+/HER2- N+ EBC

iDFS Recruiting April, 2021

NCT03726879

IMpassion050 Neoadj: atezolizumab + ddAC followed by atezolizumab + paclitaxel + trastuzumab + pertuzumab Adj: atezolizumab + trastuzumab + pertuzumab

Neoadj:

placebo + ddAC followed by placebo + paclitaxel + trastuzumab + pertuzumab

Adj: placebo + trastuzumab + pertuzumab

3 Neoadjuvant/Adjuvant HER2+

Known PD-L1 status

pCR Note: Participants

who do not achieve pCR have

the option of receiving blinded atezolizumab + T-

DM1

Recruiting April 21, 2021

NCT02926196

A-Brave Avelumab after

Adjuvant CT No Intervention after Adj CT

3 Adjuvant/Post- Neoadjuvant High-risk TNBC

EBC, LABC

DFS Recruiting June, 2021

NCT03858322

ADVANCE Arm 1: Paclitaxel + Carboplatin

Arm 2: Paclitaxel + Cyclophosphamide

n.a. 1 Adjuvant

HR+/HER2-

≥ 70 yrs at enrollment

Toxicity Receipt of Planned Therapy

Recruiting June 21, 2021

NCT02488967 AC followed by carboplatin + weekly Paclitaxel

AC followed by weekly Paclitaxel

3 Adjuvant

N+ or High-Risk N- TNBC

iDFS Recruiting July, 2021

NCT03498716

IMpassion030 Atezolizumab + CT CT 3 Adjuvant

TNBC Confirmed tumor PD-L1 evaluation

iDFS Recruiting January 15, 2022

NCT03587740

ATOP T-DM1 n.a. 2 Adjuvant

HER2+

≥ 65 yrs at enrollment EBC and LABC

NCT03561740

SMART Metronomic

Capecitabine No Intervention 3 Adjuvant HER2+

High-risk EBC

iDFS Recruiting June 15, 2023 NCT03756298 Atezolizumab +

Capecitabine Capecitabine 2 Adjuvant/Post- Neoadjuvant with

residual disease TNBC EBC and LABC

NCT03876886 AC-T

(dose-dense) TP

(dose-dense) 3 Adjuvant

TNBC and HRD 3-years DFS Recruiting February, 2024 NCT03820830

POLAR Palbociclib + ET ET 3 Adjuvant

HR+/HER2- Isolated Locoregional

Recurrence

iDFS Recruiting May 1, 2024

NCT03609047

Appalaches Palbociclib + ET CT followed by

ET 2 Adjuvant

ER+/HER2- Age ≥70 years

distant RFS Recruiting June 13, 2024 NCT03562637 Adagloxad simolenin +

OBI-821 Placebo 3 Adjuvant/Post-

Neoadjuvant with residual disease TNBC high-risk EBC

iDFS Recruiting November 30, 2025

NCT03701334

NATALEE Ribociclib + ET ET 3 Adjuvant

HR+/HER2- iDFS Recruiting December

26, 2025 NCT02954874 Pembrolizumab observation 3 Adjuvant, with

Residual Disease after neoadjuvant

TNBC or low-ER/equivocal

HER2

iDFS Severity of fatigue

Physical function

Recruiting May 31, 2026

NCT03725059 KEYNOTE-

756

Neoadj:

Pembrolizumab+CT Adj:

Permbrolizumab+ET

Neoadj:

Placebo + CT Adj: Placebo +

ET

3 Neoadjuvant/Adjuvant ER+/HER2-

tpCR Rate; EFS Recruiting January 24, 2031

NCT04109066 CheckMate

7FL

Nivolumab + neoadj CT and Nivolumab +

adj ET

Placebo + neoadj CT and Placebo +

adj ET

3 Neoadjuvant/Adjuvant High-risk BC

EBC, LABC

pCR EFS

Recruiting June 20, 2032

NCT01853748

ATEMPT T-DM1 Paclitaxel and

HER2+ DFS Active,

not recruiting

January, 2020 NCT03078751

EarLEE-1 Ribociclib + ET n.a. 2 Adjuvant

HR+/HER2- High-risk EBC

Tolerability/

Safety Active,

not recruiting

March 5, 2020

NCT02513394

PALLAS Palbociclib + ET ET 3 Adjuvant

ER+/HER2- iDFS Active,

not recruiting

September, 2020 NCT03716180

DAPHNe Paclitaxel+

Trastuzumab+ n.a. 1 Adjuvant/Post-

Neoadjuvant Adherence after

tpCR Active,

not January 1, 2021

(9)

Pertuzumab HER2+ recruiting NCT03155997

monarchE Abemaciclib + ET ET 3 Adjuvant

HR+/HER2- iDFS Active,

not recruiting

April 12, 2021

NCT01674140 ET + everolimus ET 3 Adjuvant

HR+/HER2- High-risk EBC

iDFS Active,

not recruiting

December, 2022 NCT01966471 Anthracycline

Followed by T-DM1 and Pertuzumab

Anthracycline followed by Trastuzumab,

Pertuzumab, and Taxane

3 Adjuvant

HER2+ iDFS Active,

not recruiting

January 31, 2024

NCT00301925

TACT2 E + Capecitabine or Acc. E + Capecitabine or

E + Acc. CMF

E + CMF 3 Adjuvant

EBC DFS Active,

not recruiting

September, 2024

NCT03036488 KEYNOTE-

522

Pembrolizumab + CT Placebo + CT 3 Neoadjuvant /Adjuvant

TNBC EBC pCR

EFS Active,

not recruiting

September 30, 2025

Supplementary Table 4. Ongoing trials in the adjuvant setting for early BC recruiting/open to MaBC patients. Clinicaltrials.gov was queried on February 5

^th

2020 for all therapeutic breast cancer trials open to male patients. Search terms included “adjuvant”, “Recruiting”, “Active, not recruiting”, “Interventional Studies”, “breast cancer”, “Studies with male participants”. Trials with unknown recruitment status or without status verification in 12 months were excluded. Abbreviations: HR+: Hormone Receptor-positive; ER+:

Estrogen Receptor-positive; HER2-: HER2-negative; DFS: Disease-Free Survival; iDFS: invasive Disease- Free Survival; CT: Chemotherapy; ET: Endocrine Therapy; tpCR: Total Pathological Complete Response;

EFS: Event-Free Survival; EBC: Early Breast Cancer; IBC: Inflammatory Breast Cancer; RFS: Recurrence- Free Survival; TNBC: Triple Negative Breast Cancer; T-DM1: Trastuzumab emtansine; A: Adriamycin; C:

links.lww.com/COON/A27

Supplementary Table 1. Risk factors associated to MaBC.

Supplementary Table 2. Multi-parameter gene expression assays trials for EBC. *male gender was an

exclusion criterion for this trial. Abbreviations: DFS: Disease-Free Survival; iDFS: invasive Disease-Free

Survival; DMFS: Distant Metastasis-Free Survival; RS: Recurrence Score.

neoadjuvant; yrs: years; yr: year; ET: endocrine therapy; CMF: cyclophosphamide, methotrexate, fluorouracil, and tamoxifen; N: Lymph Node status; mut: mutated; HR+: Hormone Receptor-positive; HER2-:

HER2-negative; DFS: Disease-Free Survival; GnRH: Gonadotropin-Releasing Hormone; OFS: Ovarian Function Suppression; F-up: Follow-up; A: Adriamycin; C: Cyclophosphamide; AI: Aromatase Inhibitor; AE:

Supplementary Table 4. Ongoing trials in the adjuvant setting for early BC recruiting/open to MaBC patients. Clinicaltrials.gov was queried on February 5

Estrogen Receptor-positive; HER2-: HER2-negative; DFS: Disease-Free Survival; iDFS: invasive Disease- Free Survival; CT: Chemotherapy; ET: Endocrine Therapy; tpCR: Total Pathological Complete Response;

EFS: Event-Free Survival; EBC: Early Breast Cancer; IBC: Inflammatory Breast Cancer; RFS: Recurrence- Free Survival; TNBC: Triple Negative Breast Cancer; T-DM1: Trastuzumab emtansine; A: Adriamycin; C:

Cyclophosphamide; T: Paclitaxel; P: Carboplatin; E: Epirubicin; HRD: homologous recombination repair

deficiency; EBC: Early-Stage Breast Cancer; LABC: Locally Advanced Breast Cancer; EFS: Event-Free

Survival; OS: Overall Survival; Acc.: Accelerated; IV: intravenous; SC: subcutaneously; FDC: Fixed Dose

Combination; neoadj: neoadjuvant; adj: adjuvant; LVEF: Left Ventricular Ejection Fraction; ddAC: dose-

dense Adriamycin Cyclophosphamide; N: Lymph Node status.