Male Breast Cancer: 
Developing Drugs for 
Treatment 
Guidance for Industry 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Oncology Center of Excellence (OCE) 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
August 2020 
Clinical/Medical 
   
Male Breast Cancer: 
Developing Drugs for 
Treatment 
Guidance for Industry 
 
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Food and Drug Administration 
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https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-
guidances 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Oncology Center of Excellence (OCE) 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
 
August 2020 
Clinical/Medical 
  Contains Nonbinding Recommendations 
 
TABLE OF CONTENTS 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 1 
III.  RECOMMENDATIONS .................................................................................................. 2 
  Contains Nonbinding Recommendations 
 
Male Breast Cancer:  Developing Drugs for Treatment 
Guidance for Industry1 
 
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on 
this topic.  It does not establish any rights for any person and is not binding on FDA or the public.  You 
can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.  
To discuss an alternative approach, contact the FDA staff responsible for this guidance as listed on the 
title page. 
 
 
 
I.  INTRODUCTION 
 
This guidance provides recommendations to sponsors regarding the development and labeling of 
cancer drugs, including biological products,2 regulated by CDER and CBER for the treatment of 
male patients with breast cancer.  
 
In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
the word should in Agency guidances means that something is suggested or recommended, but 
not required. 
 
 
II.  BACKGROUND 
 
Breast cancer is rare in males, with less than one percent of all breast cancer cases occurring in 
male patients.  In addition, males are more likely to be diagnosed at an older age, with a more 
advanced stage of disease, and are more likely to have lymph node involvement compared to 
females with breast cancer.   
 
Males have historically been excluded from clinical trials of breast cancer drugs because breast 
cancer in males is rare.  This exclusion has resulted in limited FDA-approved treatment options 
for males with breast cancer.  Treatment strategies for males with breast cancer are not based on 
data from prospective, randomized clinical trials.  Rather, clinical management of male breast 
cancer is generally based on clinical experience with breast cancer in females and data from 
studies conducted in females with breast cancer.  
                                                 
1 This guidance has been prepared by the Oncology Center of Excellence, the Center for Drug Evaluation and 
Research (CDER), and the Center for Biologics Evaluation and Research (CBER) at the Food and Drug 
Administration.  
2 For the purposes of this guidance, references to drugs include drugs approved under section 505 of the Federal 
Food, Drug, and Cosmetic Act (21 U.S.C. 355) and biological products licensed under section 351 of the Public 
Health Service Act (42 U.S.C. 262). 
  1  Contains Nonbinding Recommendations 
 
III.  RECOMMENDATIONS 
 
FDA encourages sponsors to discuss their breast cancer drug development plan early in 
development with CDER or CBER, as applicable.  These discussions may include expectations 
related to the number of male patients and data in male patients for specific development 
programs.  FDA recommends the following: 
 
  Eligibility criteria for clinical trials of breast cancer drugs should allow for inclusion of 
both males and females 
 
  Scientific rationale should be included in the protocol when proposing to exclude 
o
males from breast cancer trials.  FDA does not intend to consider low expected 
accrual rates of male patients with breast cancer to be a sufficient scientific 
rationale for excluding them from a clinical trial. 
 
  When males have not been included or when inclusion of males is very limited in clinical 
trials for a specific breast cancer drug:  
 
  It may be possible to extrapolate findings to include male patients in the FDA-
o
approved indication for the drug where no difference in efficacy or safety is 
anticipated between males and females based on the mechanism of action of a 
drug.  The use of extrapolation should be supported by, for example, data from 
earlier stages of development (e.g., nonclinical testing), literature, or both. 
 
  Further clinical data may be necessary to support extrapolation of findings to 
o
support an FDA-approved indication for male patients with breast cancer where 
there is a concern for differential efficacy or safety between males and females.  
In breast cancer, this may be relevant when a drug results in or relies upon 
manipulation of the hormonal axis, as with endocrine therapy.  The additional 
data to support efficacy and safety for male patients with breast cancer can be 
generated through a variety of trial designs using different data sources, including 
small single-arm trials and studies using real-world data sources. 
 
  In general, when males are included in clinical trials evaluating breast cancer drugs, 
sponsors should conduct nonclinical general toxicology studies in male and female 
animals.3, 4   
                                                 
3 For nonclinical data needed to support clinical trial design and marketing applications, refer to ICH guidance for 
industry S9 Nonclinical Evaluation for Anticancer Pharmaceuticals (March 2010), ICH guidance for industry S9 
Nonclinical Evaluation for Anticancer Pharmaceuticals Questions and Answers (June 2018), and guidance for 
industry Oncology Pharmaceuticals: Reproductive Toxicity Testing and Labeling Recommendations (May 2019).  
We update guidances periodically.  For the most recent version of a guidance, check the FDA guidance web page at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents. 
4 The Agency supports the principles of the 3Rs to reduce, refine, and replace animal use in testing when feasible. 
Sponsors can consult with the Agency if they wish to use other testing methods or strategies.  The Agency will 
consider whether such an alternative method or strategy could be used instead of an animal study. 
 
  2