International Journal of
Radiation Oncology
BRIEF OPINION
Breast and Prostate Cancer: Lessons to Be Shared
Daniel E. Spratt, MD,* and Reshma Jagsi, MD, DPhil*,y
*Department of Radiation Oncology and yCenter for Bioethics and Social Sciences in Medicine,
University of Michigan, Ann Arbor, Michigan
Received Dec 5, 2016, and in revised form Jan 30, 2017. Accepted for publication Feb 8, 2017.
Each year, 500,000 Americans receive new diagnoses of
either breast cancer (the most common cancer among US
women) or prostate cancer (the most common cancer
among US men). In 2010, 22% of the staggering $125
billion in cancer care costs was spent on these 2 cancers
alone. Both cancers generally have a long natural history
compared with other malignancies, and the parallels extend
far beyond sheer epidemiology and impact (Table 1).
Breast cancer and prostate cancer are classic examples
of hormonally dependent cancers. George Beatson, more
than 100 years ago, and Charles Huggins, 50 years ago,
demonstrated that surgical castration improved outcomes
for metastatic breast and prostate cancer patients. In the
past 30 years, drug development has focused on chemical
forms of castration and targeting the estrogen and androgen
receptors. Genomically, germline and somatic BRCA mu-
tations and other defects in DNA repair have been shown to
be frequently present in breast and prostate cancer.
Radiation therapy has been used for more than 100 years
for the treatment of breast and prostate cancer (Fig. 1), and
many of the technological advancements in radiation therapy
have been inspired by optimizing treatment of these dis-
eases. Perhaps no medical specialists are better positioned to
learn from the parallels between breast cancer and prostate
cancer than radiation oncologists, who are far more involved
in the management of both diseases than the separately
trained groups of surgeons or medical oncologists. For this
reason, radiation oncologists are uniquely suited to appre-
ciate the intricacies in the history and management of both
Reprint requests to: Reshma Jagsi, MD, DPhil, Department of Radia-
tion Oncology, University of Michigan, UHB2C490, SPC 5010, 1500 E
Medical Center Dr, Ann Arbor, MI 48109-5010. Tel: (734) 936-
7810; E-mail: rjagsi@med.umich.edu
Conflict of interest: D.E.S. reports no relevant conflicts of interest but
reports research outside this work was funded by the Prostate Cancer
Int J Radiation Oncol Biol Phys, Vol. 98, No. 2, pp. 263e268, 2017
0360-3016/$ - see front matter 2017 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.ijrobp.2017.02.015
biology physics
www.redjournal.org
breast and prostate cancer given our fundamental role in the
treatment of both diseases.
Of note, despite similarities in biology, incidence, and
outcomes, the paths taken by the oncologic community in
the management and investigation of these 2 cancers have
diverged in a number of ways. Because the differences that
have developed in the approaches to these 2 diseases seem
inadequately explained by differences in clinical features
alone, they merit reflection. These differences likely have no
single overarching explanation but rather reflect the magni-
fication of subtle clinical differences by the complex inter-
play with societal and professional cultures, gender norms,
financial incentives, and more. By explicitly comparing and
contrasting the approach to breast and prostate cancer, we
seek to generate insights whereby seemingly insurmountable
obstacles in one may be identified as mutable targets for
change by a more heartening experience in the other.
Moreover, by reflecting on the potential drivers of common
challenges confronted across the 2 diseases, we seek also to
identify the most efficient targets for interventions to pro-
mote the quality of care in both fields.
The Two Approaches
Breast cancer
Paramount in the treatment of breast cancer is the strong
focus on multidisciplinary care. The landmark paradigm
Foundation and the Department of Defense. R.J. reports no relevant con-
flicts of interest but reports research outside this work was funded by the
National Institutes of HealtheNational Cancer Institute (R01 and P01
grants), the Doris Duke Foundation, and Blue Cross Blue Shield of
Michigan.
264 Spratt and Jagsi International Journal of Radiation Oncology  Biology  Physics

Table 1 Similarities and differences in breast and prostate cancer

Breast cancer Prostate cancer
Epidemiology
Incidence 249,260 180,890
Mortality 40,890 26,120
% mortality 16 14
Lifetime risk 1 in 8 1 in 8
Cancer-specific survival
In situ (20 y) >99% >99%
Early stage (10 y) >95% >95%
Node positive (10 y) 85% 60%-80%
Metastatic (5 y) 26% 29%
Screening
USPSTF recommendation B (offer or provide this service) D (discourage use of this service)
Treatment
in situ S plus RT with or without ET Obs
Early stage S plus RT with or without ET with or without Obs/AS or RT or S
CT with or without aHer2
T3N0 S plus RT with or without ET with or without Most common: S alone
CT with or without aHer2 Recommended: RT plus ADT or S plus
RT
Node positive S plus RT plus CT with or without ET with or ADT or RT plus ADT
without aHer2
Terminology
In situ disease Stage 0 Not included in staging
Early stage Stage I-IIA favorable or unfavorable biology Very low risk or low risk
Clinical trial focus
Nonmetastatic
Node positive
Salvage treatment
Metastatic
Primary oncologic focus
Local control
Overall survival
Short-term toxicity
Long-term toxicity
Funding
Government $891 million (2010) $399 million (2010)
American Cancer Society $88 million $43 million
Abbreviations:ADT Z androgen deprivation therapy; AS Z active surveillance; aHER2 Z anti-Her2; CT Z chemotherapy; ET Z endocrine therapy;
Obs Z observation; RT Z radiation therapy; S Z Surgery; USPSTF Z US Preventive Services Task Force.

shift away from the Halstedian approach of radical surgery
and toward breast-conserving therapy that occurred over
3 decades ago (1) has been complemented by adoption of
breast cancer screening for earlier detection, implementa-
tion of the sentinel lymph node biopsy for axillary
management, identification of ER and HER2-targeted
therapies, use of companion genomic tests to personalize
the use of chemotherapy, and investigations of accelerated
and hypofractionated courses of radiation therapy to reduce
the burden of adjuvant therapy for early-stage disease. The
support of multimodality care by the breast cancer
community has allowed for hundreds of large randomized
clinical trials to be conducted, many in the localized disease
setting, that rigorously evaluate the benefit and harm of
each therapy (and combinations thereof). The oncologic
goals in nonmetastatic breast cancer have been primarily
focused on achieving local-regional control and minimizing
late treatment-related morbidity. Significant improvements
in distant metastasisefree survival or overall survival have
not been considered mandatory for the adoption of
additional therapies in this disease setting (eg, adjuvant
radiation therapy for ductal carcinoma in situ [DCIS],
tumor bed boosts, and comprehensive nodal irradiation).
Although there have been some indications that practice
can be slow to change, the evolution of evidence has
uncontrovertibly had a dramatic impact on the options
patients with breast cancer are offered today.
Prostate cancer
In contrast, patients with nonmetastatic prostate cancer
today are treated most commonly with single-modality
local therapy; in 2016 this was most frequently by radical
Volume 98  Number 2  2017 Breast and prostate cancer lessons 265

Total mastectomy and ALND

Sentinel lymph node biopsy Omission of ALND for select
Halsted radical mastectomy initially reported
Surgery Breast conserving therapy N+ patients

Radium implants Hypofractionation safe APBI guidelines published

Interstitial breast brachy tested
Radiotherapy Adjuvant whole breast
2D radiotherapy radiotherapy Tumor bed boost beneficial Simple IMRT/3D conformal Comprehensive nodal
radiotherapy beneficial radiotherapy beneficial
Breast Cancer

Adjuvant chemotherapy (CMF) Paclitaxel approved

Chemotherapy Neoadjuvant chemotherapy Docetaxel approved
Anthracyclines beneficial
beneficial
Tamoxifen for invasive breast Tamoxifen for DCIS beneficial
Hormonal Therapy Oophorectomy Letrozole and exemestane Benefit of longer endocrine
cancer beneficial approved therapy
Anastrozole approved
Targeted Therapy Trastuzumab approved Pertuzumab approved

Companion genomic tests

Screening/Biomarkers Clinical breast exam Mammography screening utilized
widespread Breast MRI increased use

Pre-1970s 1970s and 1980s 1990s 2000s 2010s

Radical perineal
prostatectomy Nerve sparing prostatectomy Robotic prostatectomy Active surveillance use
Surgery Radical retropubic increases
prostatectomy
Dose escalation beneficial Hypofractionation safe
Radium implants Ultrasound guided Intensity modulated
Radiotherapy
Prostate Cancer

brachytherapy developed 3D conformal radiotherapy radiotherapy widespread

2D radiotherapy Image guided radiotherapy
widespread widespread
Chemotherapy Docetaxel beneficial post-RT
for high risk PCa

Benefit of adding ADT to RT LHRH antagonists approved Benefit of ADT with salvage RT
Hormonal Therapy Orchiectomy Leuprolide and Flutamide
approved Bicalutamide approved Benefit of longer ADT after RT Benefit of ADT with dose
escalated RT
Targeted Therapy
USPSTF recommended against
Screening/Biomarkers Digital rectal exam PSA discovered PSA screening widespread
PSA screening

Fig. 1. Historic developments in management of breast and prostate cancers. Abbreviations: ADT Z androgen deprivation
therapy; ALND Z axillary lymph node dissection; APBI Z accelerated partial breast irradiation; brachy Z brachytherapy;
CMF Z cyclophosphamide, methotrexate, and 5-fluorouracil; DCIS Z ductal carcinoma in situ; IMRT Z intensity
modulated radiation therapy; LHRH Z luteinizing hormone-releasing hormone; MRI Z magnetic resonance imaging;
PCa Z prostate cancer; PSA Z prostate-specific antigen; RT Z radiation therapy; 3D Z 3-dimensional; 2D Z 2-
dimensional; USPSTF Z US Preventive Services Task Force.

prostatectomy. Many of the advances in prostate cancer
over the past decade have been in the metastatic setting,
and there have been fewer randomized trials conducted in
localized prostate cancer. Cytotoxic chemotherapy has only
very recently demonstrated positive results in castration-
sensitive metastatic disease and in high-risk nonmetastatic
patients. Furthermore, practice patterns often do not reflect
adoption of the results from trials that have been conducted
(eg, use of adjuvant radiation therapy after prostatectomy or
inappropriate use of androgen deprivation monotherapy for
high-risk prostate cancer). In fact, radical prostatectomy
has principally been unchanged over the past 35 years since
Patrick Walsh described the functional-anatomic approach
with nerve-sparing prostatectomy. Nevertheless, the pros-
tate cancer community has done a remarkable job in un-
derstanding and accepting that not all cancer warrants
immediate treatment and that the treatment may be worse
than the disease. For example, in situ disease and low-risk
invasive disease are unlikely to reduce the quantity or
quality of life of a patient, and treatment recommendations
commonly are either no treatment (termed observation) or
deferred treatment (termed active surveillance) (2). This
also is reflected in part by the US Preventive Services Task
Force D recommendation against prostate-specific
antigen screening. The primary oncologic focus in prostate
cancer is divided by urology and radiation oncology, where
the former is principally focused on short-term treatment-
related morbidity whereas the latter is focused more on
long-term quality of life and improvements in overall
survival.
These large differences in the treatment approaches of
breast and prostate cancer can help to identify lessons that
each community can learn from the other (Table 2).
Lesson 1: Terminology
The terminology used to convey a diagnosis to a patient has
been shown to be of great importance in a patients un-
derstanding of the severity of his or her disease. For
example, DCIS of the breast, also termed stage 0 breast
cancer, is viewed by patients as just that, cancer. It is also
treated as aggressively as most stage 1 breast cancers, with
bimodality or trimodality therapy consisting of surgery,
adjuvant radiation therapy, and potentially, hormone
therapy. Currently, with treatment, <1% of patients with
DCIS die of breast cancer over a 20-year period. Yet, we
see rising rates of mastectomy and even contralateral
266 Spratt and Jagsi
Table 2 Cross-fertilizing ideas: Obstacles and possible solutions
Obstacles
Obstacles in breast cancer
Overtreatment: Many women receive aggressive
treatmentsdincluding bilateral mastectomydwithout
clear clinical benefit.
Focusing on local control and age rather than life expectancy
exacerbates the tendency toward overtreatment.
Obstacles in prostate cancer
Undertreatment and slow diffusion of evidence into
practice
There is a need for better evidence regarding comparative
effectiveness of different approaches.
prophylactic mastectomy being pursued by women with
DCIS in the hopes of achieving peace of mind.
In contrast, in situ disease of the prostate, termed high-
grade intraepithelial neoplasia, intentionally does not carry
a cancer diagnosis and does not necessitate treatment.
Likewise, there was recently a significant change in pros-
tate cancer grading to, in part, develop nomenclature that
supports the indolent nature of low-grade disease, changing
Gleason 6 prostate cancer to grade 1 cancer. There is even
mixed support to remove the cancer designation from
grade 1 prostate cancer, especially because treatment in
many of these patients is more likely to result in morbidity
than improvements in quantity of life.
It has been increasingly recognized that the discordance in
terminology and management for in situ disease of the breast
may inadvertently lead to the overtreatment of patients
whose disease would never cause harm (3). Although there
remain substantial challenges in identifying which patients
with DCIS might safely avoid immediate treatment, this is an
important subject of ongoing investigation, and we believe
that the breast cancer community can learn from the prostate
cancer community to adopt terminology that may better help
patients and practitioners understand the nature of patients
disease and make decisions to avoid overtreatment.
Lesson 2: Life Expectancy
The management of early-stage breast and prostate cancer is
also remarkably different. A fundamental feature of the Na-
tional Comprehensive Cancer Network guidelines for men
with prostate cancer is the incorporation of life expectancy
into treatment recommendations. In fact, if a patient has a
<10-year life expectancy for low-risk prostate cancer,
observation is the recommended treatment. In contrast,
active surveillance or observation is not a currently recom-
mended treatment option for any stage of breast cancer, not
even for stage 0 disease, although research is ongoing in this
International Journal of Radiation Oncology  Biology  Physics
Potential solutions
Potential solutions from prostate cancer
Terminology: The panic associated with diagnosis can be
tempered by considering carefully what one calls in situ
disease and how one grades invasive cancer.
Focusing on overall survival and incorporating considerations
of life expectancy into decision making can be powerful
mechanisms by which to combat overtreatment.
Potential solutions from breast cancer
Professional culture: There is a strong culture of
multidisciplinary care in which physicians become more
aware of the evidence regarding treatment modalities they
themselves do not deliver.
Societal culture: Engaging patient advocates and the public is
a powerful way to generate needed resources and encourage
willingness to participate in trials.
area. The goal of treatment should be to increase the quality
and/or quantity of life, not simply to improve on the already
high rates of local-regional control achieved in early-stage
breast and prostate cancer. It is increasingly recognized that
our treatments have morbidity associated with them,
including financial toxicity, cardiac toxicity, lymphedema,
erectile dysfunction, urethral stricture, hematochezia, and
morbidity from hormone therapy, some of which may be life
shortening. We should offer treatment to those patients we
expect to benefit from our therapies, and we must recognize
that most of the survival benefit for the treatment of early-
stage disease occurs likely beyond 10 years after treatment.
Although older patients may also value reduction in the risk of
local recurrence to avoid additional surgery and associated
distress, 5-year rates of local recurrence for select patients
with favorable-risk breast cancer are quite low even without
radiation therapy, suggesting that omission of radiation ther-
apy should be considered in patients with limited life expec-
tancy who have lower-risk disease. Incorporation of age into
decisions to omit adjuvant radiation therapy for breast cancer
should be seen as just the tip of the iceberg, and further
incorporation of life expectancy and comorbidity status is
sorely needed to ensure nonmaleficence in this setting (4).
Lesson 3: Acceptance of Multimodality Care
Just as it is critical to avoid overtreatment of patients with a
favorable prognosis and short life expectancy, undertreat-
ment of patients with more aggressive disease is a serious
concern. Women with locally advanced breast cancer are
often treated with multiagent neoadjuvant chemotherapy,
surgery, nodal evaluation, and comprehensive nodal radia-
tion therapy. Many women are also treated with anti-HER2
therapies and 5 to 10 years of hormone therapy. In contrast,
among men with high-risk prostate cancer who undergo
radical prostatectomy, >85% of patients receive no other
form of adjuvant treatment (5). It is unsurprising that this
Volume 98  Number 2  2017
has been shown to result in a 50% chance of subsequent
progression 5 years postoperatively. Furthermore, node-
positive prostate cancer is most commonly treated with
androgen deprivation therapy alone, a noncurative therapy.
The root cause of these differences in the management
of locally advanced prostate cancer is unclear but may
relate to differences in the historical development of
interspecialty cooperation across the fields. Pioneering ef-
forts for breast conservation married surgeons and radiation
oncologists to one another long ago in the quest for local
control; perhaps because radiation therapy has not been
offered as a single-modality local treatment, breast sur-
geons have not viewed radiation oncologists as competitors
but rather as key collaborators with shared goals. In
contrast, partnerships between urologists and radiation
oncologists have been less common, and competition for
patients (encouraged by a health care system that heavily
rewards the physician who provides a treatment interven-
tion over physicians who assist in the evaluation,
management, and decision-making process) may compli-
cate relationships, although cooperation has been admirably
nurtured in creative ways. The history of multidisciplinary
cooperation in breast cancer has created a virtuous cycle,
whereby these relationships are strengthened by the mutual
generation of high-quality data in randomized trials to
establish consensus regarding unified treatment approaches
for high-risk disease. The appallingly low rates of radiation
therapy use in patients with high-risk prostate cancer (with
approximately 10% receiving adjuvant radiation therapy
with T3 disease or positive margins and <20% of patients
with a rising prostate-specific antigen level postoperatively
undergoing salvage radiation therapy) suggest that building
a culture of mutual respect and cooperation across the
different specialties that manage prostate cancer is of crit-
ical importance to the patients we serve.
Of note, the ProtecT (Prostate Testing for Cancer and
Treatment) trial has demonstrated that randomization
between surgery and radiation therapy is possible, and such
a trial for men with high-risk prostate cancer is critically
needed to potentially help establish a risk-based standard of
care. In the meantime, one method to improve the use and
acceptance of multimodality care is through routine use of
multidisciplinary clinics where all patients with a diagnosis
of prostate cancer are seen by both a urologist and a radi-
ation oncologist. This framework is already commonplace
in many breast cancer clinics and may aid in removing
obstacles to multidisciplinary care.
Lesson 4: Sociocultural Factors and Funding
The sociocultural aspects of these 2 diseases are markedly
different and have played an important role in the philan-
thropic and community support necessary for advancements
made in the management of nonmetastatic disease. From the
pink ribbon to the pink shoes worn by national sports teams,
October is widely recognized as Breast Cancer Awareness
Breast and prostate cancer lessons 267
Month. Although unknown to many, the parallel Prostate
Cancer Awareness Month is September. Widespread public
awareness and support are critical to create an environment
that promotes patient enrollment in clinical trials and fund-
ing for research. Indeed, despite the difficult national
research funding climate, the breast cancer community has
been relatively effective in advocating for support. In 2010
breast cancer research received $891 million of federal
funding in the United States whereas prostate cancer
received $399 million, and similar trends are seen from
private funding sources such as the American Cancer
Society ($88 million vs $43 million). The growing reliance
on industry for biomedical research funding (6) and the
inadequate representation of those from fields such as radi-
ation oncology (7) and surgery among principal investigators
of federally funded studies are particularly challenging when
the overall budget is smaller, as it is in prostate cancer.
Beyond the issues related to interspecialty collaboration
discussed earlier, these differences in research funding may
also help to explain why the majority of funding efforts for
prostate cancer have focused on the metastatic setting, where
5 new therapies have recently gained Food and Drug
Administration approval. Ultimately, without broader public
awareness and support, prostate cancer research may suffer
from critical potential advances in management.
Efforts from Movember and the Prostate Cancer Foun-
dation continue to make progress in increasing social
awareness and have become the largest philanthropic sour-
ces of funding for prostate cancer research. Further advocacy
is needed to increase government funding of biomedical
research in general and regarding prostate cancer in partic-
ular. Of note, improving multidisciplinary cooperation be-
tween urologists and radiation oncologists may not only
improve patient management but also aid in more effective
lobbying for support that is necessary to improve the evi-
dence base for decision making by men with prostate cancer.
Summary
In recent years, much attention has focused on the concept
that cancer is a heterogeneous collection of diseases, and
rightly so. However, there is also much to learn by consid-
ering the commonalities that supersede these differences
(Table 3). Radiation oncologists are uniquely situated to
Table 3 Obstacles shared by breast and prostate cancer
Resistance to using hypofractionation (likely partly because
of trepidation about toxicity and partly because of financial
disincentives)
Rapid uptake of more expensive technologies without evidence
of increased value (likely related to financial incentives)
Overuse of treatments in patients with favorable prognosis
Underuse of treatments in patients with advanced disease
Limited patient knowledge, which compromises shared
decision making
268 Spratt and Jagsi
point out both the parallels and the distinctive features in the
rich history of research and management of breast and
prostate cancers. Physicians, researchers, and patients alike
may benefit from considering the tremendous achievements
within each field and attempting to replicate those successes
in the other. The 4 lessons presented are just a few of many
lessons that each community can learn from the other. As the
importance of value-driven care and shared decision making
is increasingly recognized, we must work together with our
colleagues to avoid both overtreatment and undertreatment,
informed by the insights that abound if we dare to cross the
boundaries of disease type.
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