1

Challenges of Diagnosing and Treating Male Breast Cancer: A Case

Study
Lee Culp R.T.(T), Andy Kressin B.S., Nishele Lenards M.S., R.T.(R)(T), FAAMD, Anne Marie
Vann, MEd, CMD, RT(R)(T), FAAMD

Abstract:
Introduction: Male breast cancer (MBC) is a rare disease, but has been on the rise in the past
decade.
1-4
Since MBC is so rare, most of the published information regarding the disease is
extrapolated from female breast cancer (FBC) data. Males have seemingly not benefitted from
the advancements leading to earlier breast cancer diagnosis and better cancer care in the same
way females have in the past decade.
3
Oftentimes, at initial presentation males are misdiagnosed,
or imaging modalities are inconclusive.
Methods: Two patients from separate institutions were chosen for this study. Upon initial
consultation and workups, both patients were informed that their presenting symptoms were not
believed to be caused by cancer, even after palpated breast exams. However, after a lumpectomy
in one patient, the specimen was found to be ductal carcinoma in situ (DCIS). The other patient
was found to have breast cancer during workup years after initial consultation.
Discussion: Mammograms and ultrasounds (US) are the standard for initial breast examination in
both men and women. However, a study by Kuhl, Schrading, Leutner, et al
13
found that magnetic
resonance imaging (MRI) used for female breast examinations was far superior to
mammography and US in detecting cancers. It has also been noted that US studies are operator
dependent and some radiologists prefer to perform their own US studies instead of interpreting
the US study of another clinician. Since males have not benefited the same from the
advancements in breast cancer comparative to women, maybe MRI studies in conjunction with
another diagnostic study should be considered for males at the time of initial examination for
breast cancer.

Introduction:
Male Breast Cancer is a rare disease accounting for only 1% of total breast cancers worldwide,
however, the incidence of MBC has been on the rise in the past 10 years.
1-4
More specifically,
2

there has been a 45% increase seen in the United States.
3
It is expected that over 2300 men will
be diagnosed in 2014 with breast cancer, including a death toll of between 400 and 500.
5
Because
of the rarity of the disease, most of the published information regarding MBC is based on small,
single institutional data or extrapolated from data regarding FBC. Traditional treatments for FBC
are the current standards of care for MBC patients.
Due to the lack of public awareness, as well as the rarity of disease, MBC is usually diagnosed in
late stages; either III or IV. As a result, MBC generally has a worse prognosis than FBC.
2,6
As is
diagnostically customary in initial workup for women, men who present with possible breast
cancer typically receive mammograms, US, MRI, fine needle aspiration (FNA), or some
combination thereof. Males have seemingly not benefitted from the advancements leading to
earlier breast cancer diagnosis and better cancer care in the same way females have in the past
decade.
3
This may be due to the greater awareness and preventative screening programs currently
in place for women. Some studies have shown that MBC diagnoses are delayed 6 to 10 months
on average.
7
Perhaps, there may need to be alternate diagnostic approaches taken when male
patients present in the clinic. Also, there are no definitive etiological risk factors known to be
responsible for the onset of MBC. However, certain criteria have been known to be linked.
The strongest link for MBC is the breast cancer 2 (BRCA2) gene mutation. The breast cancer 2
gene is a gene that produces tumor suppressing proteins. These proteins aid in repairing damaged
DNA. When these genes are mutated, the damaged DNA may not be repaired accurately.
8

BRCA2 increases the overall risk of breast cancer for both men and women. Nonetheless,
women statistically present more often with BRCA1, while MBC BRCA1 mutations are
uncommon. Due to genetic differences between male and female breast cancers, should different
diagnostic approaches be taken when males present with breast cancer symptoms?
Methods:
Two male breast cancer patients receiving treatment in two different locations across the United
States were compared in this study. One patient was treated in Buffalo, NY (patient DF), while
the other patient was treated in La Crosse, Wisconsin (patient PP). Both patients presented with
abnormalities in their breasts, and both were initially informed that their concerns were not
cancerous. However, after later follow up visits regarding their chest issues, as well as numerous
imaging studies and procedures, both men were determined to in-fact have MBC.
3

Patient DF is a 57 year old male who presented in December of 2013 with a sudden onset of
moderate pain in his left breast. At the time of his initial consult, the pain had been present for
two months, and he described it as shooting and sore to the touch but not radiating. DF also
denied any associated mass, nipple discharge, axillary lump, axillary swelling, or skin changes.
He believed the pain was due to a change in activity or exercise, where the pain was alleviated
by medication and rest. During initial consultation, a breast exam was performed while DF was
standing, in the supine position, and in a sitting position. The breasts were found to be normal on
inspection, with no skin changes. However, the left breast was found to be tender, with no
dominant mass noted. At the time of initial consult, a bilateral mammogram (Figures 1 and 2)
was completed with findings of the left side having a focal density in the retroareolar region, and
two 5 mm adjacent lymph nodes at the lateral aspect of the left breast. The US finding
demonstrated a 2.2 cm ill-defined retroareolar area, likely a focal mastitis with no definite lump
or erythema (Figures 3 and 4). Final assessment from the initial mammogram and ultrasound was
Breast Imaging-Reporting & Data System (BI-RADS) category 3; probably benign. The BI-RAD
system was developed by radiologists for reporting mammogram results using a common
language. A BI-RADS of category 3 means that the mammogram is probably normal, but a
repeat mammogram should be completed in 6 months. The chance of breast cancer is
approximately 2% in this category.
9
A chest x-ray was also completed at this time showing no
invasion into the chest (Figure 5).

In January of 2014, one month later, DF had a follow-up US of the left breast. This US study
revealed the previously noted changes in the left retroareolar region once again, but they
appeared less prominent. This time the density was found to measure 1.6 cm. The previously
mentioned lymph nodes measured 5 mm again. In February 2014, the patient had another
consultation regarding the pain that still resided in his left breast. Pathology at this appointment
was found to show gynecomastia and focal atypia with no evidence for malignancy. Another
series of breast exams were performed, with no dominant masses noted. A MRI was ordered for
further evaluation which showed no evidence of active disease. At this point, excision was
recommended to DF, along with a partial mastectomy. The patient declined partial mastectomy
and elected to have a lumpectomy in late February 2014.
A biopsy was completed on the mass after the lumpectomy excision, and was determined to be
Ductal Carcinoma in Situ (DCIS) with a nuclear grade of 1 to 2, measuring 4.7 mm. No lymph
4

nodes were taken for sampling. Necrosis was not detected in the sample, and margins were
negative. The architectural pattern of the DCIS was that of cribriform. With cribriform
carcinoma, the cancer cells invade the stroma (connective tissues of the breast) in nest-like
formations between the ducts and lobules. Within the tumor, there are distinctive holes in
between the cancer cells. Cribriform carcinoma is usually low grade, meaning that its cells look
and behave somewhat like normal, healthy breast cells.
10
Estrogen and progesterone receptor
(ER/PR) assays were performed, and both receptors were found to be positive.
Patient PP is a 73 year old male who presented at an outside institution in August 2009 with left
nipple drainage but no palpable lump. In August 2009, PP underwent a mammogram and an
ultrasound of the left breast (Figure 6 and 7). The mammogram showed a 4 mm indeterminate
density, while the ultrasound showed no sonographic evidence of malignancy. Patient PP was
noted to have gynecomastia in both breasts. In March 2010, PP was seen for follow-up and was
found to have a new 1.5 x 1 cm lump in the 4 oclock position of the left breast. The patient
underwent an additional mammogram and ultrasound. The mammogram showed no abnormality
in the left breast corresponding to the palpable lump. Ultrasound also showed no sonographic
abnormalities in the left breast. The patient returned for follow-up in June 2010, and was found
to have no more bloody discharge and no palpable abnormalities. In March 2014, the patient
presented with a self-identified lump in the left breast that had been problematic. A diagnostic
bilateral mammogram was completed in March 2014 (Figure 8). This showed a 4 cm density in
the upper inner quadrant of the left breast. In the same month, the patient underwent a left breast
ultrasound (Figure 9). The ultrasound showed a hypoechoic mass corresponding to the location
of the palpable lump. Some margins demonstrated nodularity with small nodules not definitely
connected to the larger mass. Therefore, the possibility of additional disease further away from
the palpable mass could not be ruled out. An ultrasound-guided biopsy took place in March 2014
and revealed intermediate grade infiltrating mammary carcinoma of no special type. The ER/PR
were positive and HER2/neu was negative. The patient underwent total left breast mastectomy
along with left axillary sentinel lymph node biopsy in late March 2014. The sentinel lymph node
was positive, leading to complete axillary dissection. A small piece of the superficial layer of the
pectoralis muscle was also removed in order to ensure an adequately deep margin. Pathology
revealed grade 2 invasive ductal carcinoma that was 3.8 cm in dimension. All margins were
negative and the final deep margin was benign skeletal muscle. Malignant cells were present in
5

the lymph nodes with 1 macrometastasis and 1 micrometastasis. The largest metastatic focus was
15 mm. A total of 44 lymph nodes were evaluated, 2 of which were positive. Extranodal
extension was present. The patient was felt to have pathologic T2N1a disease. The patient
underwent genetics evaluation and was advised to have genetic testing. Genetic tests were
negative for BRCA1 and BRCA2 mutations.
In March 2014, the patient was referred to radiation oncology for post-operative radiation
therapy of the left chest wall. Post-surgery radiotherapy can decrease local recurrence in patients
with high-risk breast cancer and improve the overall survival rate.
11
The radiation oncologist
reviewed the patients records and discussed various treatment regimens with PP. Radiation
therapy to the left chest wall and regional lymph nodes was recommended. The radiation
oncologist discussed the benefits and side effects of chest wall and lymph node irradiation. The
patient elected to proceed with the radiation therapy treatments.
Diagnostic Imaging
Patient DF completed a mammogram in December of 2013 which was interpreted as negative. In
January 2014, DF had a follow-up US to the left breast. The follow-up US showed the previously
noted changes in the left retroareolar region but appeared less prominent as the density measured
1.6 cm as opposed to the previous 2.2 cm. The lymph nodes previously mentioned measured the
same as before; 5 mm. In February 2014, the patient had another consultation regarding the pain
that still resided in his left breast. An MRI was ordered for further evaluation but showed no
evidence of active disease.
In August 2009, PP underwent a mammogram and an ultrasound of the left breast at an outside
institution. The mammogram showed a 4 mm indeterminate density, while the ultrasound
showed no sonographic evidence of malignancy. PP was noted to have gynecomastia in both
breasts. In March 2010, PP was seen for follow-up and was found to have a new 1.5 x 1 cm lump
in the 4 oclock position of the left breast. The patient underwent an additional mammogram and
US. Neither mammogram nor US revealed abnormalities corresponding to the palpable lump. In
early March 2014, PP underwent a bilateral mammogram that revealed a density in the upper
inner quadrant of the left breast. In the same month, the patient underwent a left breast US. This
revealed an irregular hypoechoic mass corresponding to the location of the palpable lump. An
US-guided biopsy took place in March 2014 which revealed mammary carcinoma, no special
type, intermediate grade that was ER and PR positive.
6

Diagnostic studies such as mammogram and US are important not only for providing insight into
the presence or absence of disease, but they also provide information regarding the extent of
disease. These images are particularly important in radiation oncology as they assist the radiation
oncologist in understanding location and size of the tumor. This information obtained from the
imaging studies plays a major role in determining the region to be focused on for radiation
treatment planning delivery.
Radiation Oncologist Recommendations
The radiation oncologist discussed with DF the treatment options of a mastectomy and breast
conservation therapy. DF refused a mastectomy, due to chest deformity concerns. They
discussed breast conservation in great detail along with the acute and chronic side effects of
radiation. After discussion of radiation side effects DF agreed to proceed. The radiation
oncologist anticipated delivering post-operative radiation therapy to the left breast followed by
an electron boost to the tumor bed.
Patient PP was informed of his many treatment options including mastectomy or lumpectomy
followed by post-operative radiation therapy. PP opted to undergo a mastectomy. He also agreed
to receive post-operative radiation therapy after a thorough discussion with the radiation
oncologist concerning the risks and potential side effects of radiation therapy treatment. The
radiation oncologist further recommended to PP that an electron boost plan treating the
mastectomy scar be added after the chest wall and lymph node irradiation.
The Plan (prescription)
The radiation oncologists plan for DF was to use hybrid intensity-modulated radiation therapy
(IMRT) due to better coverage of the planning target volume (PTV), increased skin dose, and
reduced toxicity to the heart. The prescription dose was 5040 cGy at 180cGy per fraction for a
course of 28 fractions followed by an electron boost of 1000 cGy to the tumor bed at 200 cGy
per fraction for 5 fractions.
The radiation oncologists recommendation to PP was a 3-dimensional (3D) plan utilizing
conventional medial and lateral tangential beams for the primary chest wall and lymph node
treatment. The prescription dose for the initial left chest wall plan was 5040 cGy at 180 cGy per
fraction for 28 fractions. The electron boost prescription dose to the mastectomy scar was 1000
cGy at 200 cGy per fraction for 5 fractions.
7

Both patients received the same radiation dose composite prescriptions delivered to their post-
surgical areas. The composite doses for both locations, including electron boosts to the post-
operative scars were 6040 cGy in 33 fractions.
Patient Setup/Immobilization
Patient DF underwent a computer tomography (CT) simulation scan in March of 2014 for
radiation therapy treatment planning. The patient was placed in the supine position on the CT
simulation couch with both arms above his head, and head turned to the right on a Civco breast
board with VacLoc (Figure 10). The breast board was placed at a 10
o
angle, utilizing the B head
holder. A triangle sponge was placed under the knees for support. The superior, inferior, medial,
and lateral borders were marked by the radiation oncologist.
During CT simulation, patient PP was placed in the supine position with a VacLoc and wing
board (Figure 11). The patients arms were above his head grasping the wing board pegs and
supported with foam wedges. The patient also had a triangle knee sponge for added comfort. The
radiation oncologist marked the superior, inferior, medial, and lateral treatment borders with
wire.
Anatomical Contouring
Patient DF's CT data set was transferred to the Varian Eclipse 11.0.3 treatment planning system
(TPS). The medical dosimetrist contoured organs at risk (OR) which included the heart, spinal
cord, right lung, left lung, total lung, and ipsilateral ribs. The carina was also contoured by the
medical dosimetrist to assist the radiation therapists in daily setup.
Patient PPs CT data set was transferred to the Philips Pinnacle 9.0 TPS. The medical dosimetrist
contoured the right lung, left lung, total lung, esophagus, spinal cord, carina, and heart. The
physician contoured the lumpectomy, axillary vessels, larynx, and the level 1, 2, and 3 lymph
nodes.
Beam Isocenter/Arrangement
The medical dosimetrist placed an isocenter for DF corresponding to approximately the middle
of the left breast (Figures 12-14). During the simulation procedure, the radiation oncologist
marked the edges of the field to assist the medical dosimetrist in finding mid-field. Four fields
from a 2100 iX Varian linear accelerator were used: 2 medial left breast fields utilizing 6 and 16
megavoltage (MV) energies with IMRT and 2 lateral left breast fields utilizing 6 and 16 MV
energies with IMRT. The use of the 16 MV energy photon beams were used to penetrate deep
8

into the tissue, while the 6 MV energy photons were used to obtain superficial coverage near the
skin surface. The 16 MV medial left breast field utilized a 30
o
wedge, while the 16 MV lateral
left breast field utilized a 45
o
wedge. The two fluence IMRT fields used multi-leaf collimators
(MLC) to block areas determined by the medical dosimetrist to help reduce dose to the heart and
ipsilateral lung (Figure 15). The radiation oncologist made final adjustments to the MLC leaves
in order to begin radiation treatment planning. The medical dosimetrist determined field sizes of
each beam in relation to the upper and lower limits set by the radiation oncologists during the
simulation, as well as to meet the goals of the desired dose distribution throughout the breast.
As for patient PP, the medical dosimetrist placed an isocenter in the medial left lung
approximately 1.3 cm from the chest wall (Figures 16-18). The right anterior oblique (RAO) and
the left posterior oblique (LPO) left chest wall fields had gantry angles of 315
o
and 134.5
o
respectively. The RAO and LPO supraclavicular fields had gantry angles of 345
o
and 169
o
respectively. All 4 fields utilized 15 MV beams from a 2100 EX Varian linear accelerator. There
were no collimator or couch rotations for any of the fields. The field size apertures for the left
chest wall fields were defined by the radiation oncologist and designed to include the entire post-
mastectomy chest wall region with an additional margin added for flash (Figures 19 and 20). The
supraclavicular field size apertures were also defined by the radiation oncologist (Figures 21 and
22).
Treatment Planning
The radiation oncologist outlined for DF the desired dose prescription and objectives for the
hybrid IMRT treatment plan. The intention was to irradiate the breast tissue with an appropriate
prescription coverage of the post-lumpectomy breast without destroying normal tissues and OR,
which the radiation oncologist reviewed, along with the dose volume histogram (DVH) (Figure
23). The prescription dose was prescribed to a point at mid-breast. Each beam was weighted
differently and delivered different percentages of the daily prescription dose. The 16 MV medial
left breast beam delivered 55 MU per day, while the IMRT medial left breast field delivered 141
MU per day. The 16 MV lateral left breast beam delivered 51 MU per day and the IMRT lateral
left breast field delivered 89 MU per day. A total of 336 MU was delivered daily. The patient
received a total of 180 cGy per day to the 96% isodose line for 28 fractions. The radiation
oncologist reviewed the created plan and noted that the V20 dose to the total lung was 2.2%, and
9

the V30 dose to the heart was 0%; both within their constraints. The plan was then approved for
treatment.
In PPs case, the radiation oncologist outlined the dose prescription along with the objective for
the 3D conformal treatment. The objective was to use parallel opposed supraclavicular fields in
conjunction with conventional tangential chest wall fields to maintain an adequate and
homogeneous dose distribution throughout the left chest wall tissue and left neck nodes, while
reducing toxicity to the heart and left lung (Figures 24-26). The radiation oncologist also
requested that the maximum dose to the axillary vessels be kept below 5292 cGy. The
prescription dose for the conventional tangential chest wall fields was prescribed to a calculation
point placed by the medical dosimetrist within the left chest wall tissue. The prescription dose for
the parallel opposed supraclavicular fields was prescribed to a different calculation point placed
by the medical dosimetrist in the upper axilla region. The patient received 180 cGy per day to
both the left chest wall and left supraclavicular regions for 28 fractions. Once adequate
prescription coverage and a homogeneous dose distribution was achieved to the left chest wall
and neck nodal volumes, the medical dosimetrist reviewed the axillary dose constraint, the
isodose lines, and the DVH (Figure 27). The maximum dose to the axillary vessels was 5288
cGy. The radiation oncologist also reviewed the plan and assigned a normalization of 100% to
both the left chest wall and left supraclavicular prescriptions of the treatment plan.
Discussion:
Both patients had initial workups that included mammogram and ultrasound studies, and both
were noted to have gynecomastia. Even when small densities were found in the initial workups,
they were considered non-malignant and the patients were instructed to closely monitor their
areas of concern for any changes. Mammograms and ultrasounds are the standard for initial
breast examination in both men and women. Mammography is used when US findings are
indeterminate. When US and mammography findings are suspicious, or if mammography
appears indeterminate for malignancy, tissue diagnosis is recommended.
12
However, a study by
Kuhl, Schrading, Leutner, et al
13
found that MRI used for female breast examinations was far
superior to mammography and US in detecting cancers. Patient DF underwent an MRI which
also failed to show malignancy. One possible explanation for the negative results of the three
diagnostic studies for patient DF is that the density was in an undetectable precancerous stage at
the time of the early workups. Unlike patient DF, patient PP never underwent an MRI. After one
10

diagnostic study for patient PP showed an abnormal density and the second study returned
negative, perhaps a third study in the form of an MRI could have been of diagnostic benefit
compared to DF.
It has also been noted that US studies are operator dependent. Some radiologists prefer to
perform their own US studies instead of interpreting the US study of another clinician. In the
case of PP, it is unknown how the initial US studies were performed and interpreted at the
outside institution. A study performed in Germany showed US to be an effective diagnostic
imaging technique for female breast cancer.
13
In the cases of patients DF and PP, ultrasound
failed to indicate any malignancies during initial screening. While operator error can happen no
matter the sex, is it possible the differing genetic makeup of MBC compared to that of most
FBCs make US studies less effective in male breast screenings?
Since MBC has been on the rise in the past decade, perhaps different imaging studies for men
need to be given more consideration in research studies.
3
Furthermore, imaging features that
would normally suggest benignity in females (US and Mammogram) are not always reliable
imaging findings in men, and further investigation is needed to distinguish a benign malignant
diagnosis.
14
Since males have not benefited the same from the advancements in breast cancer
screening and treatment compared to women because of the lack of the assumption of MBC,
maybe MRI studies in conjunction with another diagnostic study should be considered for males
at the time of initial examination for MBC. The answer may be as simple as performing MRI and
mammograms instead of US and mammograms. The research from Kuhl, Schrading, Leutner, et
al
13
found that all the breast cancers in their study were found if MRI was used in conjunction
with mammography. Obviously, the cost of the diagnostic study should be considered. However,
there still may be a different diagnostic study or combination of studies besides the traditional
mammogram and US arrangement that could provide for earlier detection of breast cancer in
males. Clearly the extrapolation from FBC data has not improved the frequency of early male
breast cancer diagnosis. With males failing to benefit from recent breast cancer advancements
and females being diagnosed more frequently in early stages, changes in the standards of
screening males with potential breast cancer need to be more seriously considered for research.
One obvious limitation of this study is that only 2 patients were considered. However, hopefully
the cases of the 2 patients presented can provide insight for the true need for further research on
the topic of MBC. With the continuing increase in incidence of MBC, there should be higher
11

number of MBC cases that can be considered for research. Research strictly focusing on MBC
patients could push for better MBC detection methods and more frequent early diagnoses. It
would also help alleviate any questions pertaining to the problems with extrapolations from FBC
data.



























12

References
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tumor: A case report. OncolLett.2014;8(1):190-192. http://dx.doi.org/10.3892/ol.2014.2111
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12. Adibelli Z, Oztekin O, Postaci H, et al. The diagnostic accuracy of mammogram and
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14

Figures
Figure 1. Mammogram image for patient DF.
15


Figure 2. Mammogram image for patient DF
16


Figure 3. Ultrasound image for patient DF.
17


Figure 4. Ultrasound image for patient DF.
18


Figure 5. Chest X-Ray for patient DF
19


Figure 6. Mammogram of patient PPs left breast August 2009.
20


Figure 7. Ultrasound image for patient PPs left breast August 2009.
21


Figure 8. Mammogram of patient PPs left breast March 2014.
22


Figure 9. Ultrasound image of patient PPs left breast March 2014.






23


Figure 10.Patient DF position on a 10
o
breast board with a VacLoc at CT simulation.


Figure 11. Patient PP position on a wing board with a VacLoc and wedges at CT simulation.

24


Figure 12. Axial view of isocenter placement in patient DF.
25


Figure 13. Coronal view of isocenter placement in patient DF.
26


Figure 14. Sagittal view of isocenter placement in patient DF.
27


Figure 15. Lateral Left Breast treatment field with MLC blocking for patient DF.

28


Figure 16. Axial view of isocenter placement in patient PP.

Figure 17. Sagittal view of isocenter placement in patient PP.
29


Figure 18. Coronal view of isocenter placement in patient PP.
30


Figure 19. RAO left chest wall treatment field with MLC blocking for patient PP.
31


Figure 20. LPO left chest wall treatment field with MLC blocking for patient PP.
32


Figure 21. LPO left supraclavicular treatment field with MLC blocking for patient PP.
33


Figure 22. RAO left supraclavicular treatment field with MLC blocking for patient PP.

34


Figure 23. DVH for patient DF


35


Figure 24. Isodose distribution of the inferior left chest wall for patient PP.

36


Figure 25. Isodose distribution of the superior left chest wall for patient PP.

37



Figure 26. Isodose distribution of the left supraclavicular area for patient PP.
38


Figure 27. DVH for patient PP. (Magenta = heart, Blue = total lungs, Green = axillary vessels,
Brown = esophagus, Light Brown = larynx, Yellow = level 1 lymph nodes, Orange = level 2
lymph nodes, Teal = Level 3 lymph nodes.