Breast Cancer in Men Margaret Thompson MD - PowerPoint Presentation

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Breast Cancer in Men

Margaret Thompson MD

Cleveland Clinic Florida

Breast Surgeon

September 25, 2018

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Breast Cancer

Highly prevalent disease

Limited to female sex in all but < 1% of cases in USA

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SEER

Cancer

Stat Facts: Female Breast Cancer

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Detection and Presentation

No studies to address the role of early detection in men

Screening mammogram has limited role in men than women

Due to anatomic & pathologic differences

≈

85% of male breast cancers are evident on P/E

Predominantly central

subareola

location

Limited volume of breast tissue

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Detection and Presentation

For most healthy patients

Periodic self-examination

Annual physical examination

For cancers detected in this way, most present with self-detected mass

Other symptoms

Nipple discharge

Ulceration

Bleeding

Skin inversion

Swelling

Breast pain

Compared with BC in women, nipple symptoms more common (48%)

R/T proximity of male BC to the nipple-areola complex (NAC)

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Detection and Presentation

Average duration of symptoms = 4-18 months

Patients with family history of breast cancer

Significantly shorter duration of symptoms = 1 month

Diagnosis delay strongly r/t lack of awareness of BC in men

Historical series shows a more advanced stage at presentation

With an associated delay in diagnosis

More contemporary series show more smaller tumor diameter at presentation

Suggesting ↑ public & professional awareness

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Differential Diagnosis

Gynecomastia

Limited to men

Hypertrophy of breast

Bilateral / unilateral

Tenderness

P/E = diffusely enlarged breast, firm /tender, overlying skin normal; nipple deformities / discharge unusual

Epidermal inclusion cyst

Lipoma

Subareola

abscess

Fat necrosis

C

hronic inflammation

H

ematomas

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Differential Diagnosis

Metastatic disease to the breast

Most common – metastatic prostate cancer

Share similar demographic features

Older patient in whom prevalence of gynecomastia is ↑

In patient with known history of prostate cancer, 3 diagnostic possibilities emerge

Gynecomastia

Metastatic prostate cancer

Breast cancer

Metastatic prostate cancer & 1

°

breast cancer have been ID in same breast following initiation of hormonal therapy for metastatic prostate cancer

Other

1

° tumors reported

Colon cancer, osteosarcoma, Ewing's sarcoma, lung cancer, lymphoma, laryngeal ca,

Malignant melanoma, Bowens ds

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Risk Factors

Age

Risk ↑ as

men

age

Average age

72 years old when

diagnosed

Family history of BC

BC risk ↑

if

other blood relatives have had BC

1 of

5 men with

BC have

a close relative, male or female, with the disease

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Epidemiology, Risk Factors & Genetics

Genetic predispositions play important role in

pts

with

fam

hx

of male BC or both male & female BC

Initial reports implicated BRCA2, to account for as many as 14% of male

pts

with inherited BC

More recent reports BRCA2 mutations account for 40% of all male BC in Iceland

BRCA1 mutations, although uncommon, may also account for familial cases of male BC

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Genetics

+ family history of BC in 1

°

relative is ID in 15% of male BC

pts

All male BC patients should consider genetic counselor consultation

Especially if they have premenopausal 1

°

relatives with

hx

of BC

Or multiple family members with BC or ovarian cancer

Men with BRCA2 mutation carry a 6.3% lifetime risk of BC

Intervention

Heightened surveillance

Chemoprevention

Prophylactic mastectomy

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Tamoxifen ↓ BC risk in women (STAR Trial)Used in treatment of male BC with good safety profile

Prevents only ER+ tumors

Predominant receptor profile in male BC

Chemoprevention

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Risk Factors

Cowden’s syndrome

Autosomal Dominant

Multiple

hemartoma

syndrome

Assoc

w/

germline

mutation

PTEN

tumor-suppressor gene

3 reported cases of Cowden’s syndrome have occurred in men

2 led to lethal BC developing while patients were in their early 40s

Multiple

lipomas

of various sizes on the torso (a), limbs (b) and on the left thumb basal joint right (c)

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Risk Factors

Klinefelter’s

syndrome

XXY karyotype hormonal condition

Hypogonadism

Gynecomastia

Aspermatogenesis

Obesity

Genetic predisposition of 20-

to 50-fold

↑

BC risk

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Risk Factors

Alcohol

↑ alcoholic intake ↑risk of male BC

Possible d/t effects on liver

Liver disease

Liver plays important role in balancing sex hormones levels

In severe liver disease (cirrhosis)

Hormone levels are uneven

Causing < levels of androgens & > estrogen levels

Men with liver disease have a > chance of developing

gynecomastia

They have > risk of developing breast cancer.

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Risk Factors

Radiation exposure

Men who have had previous chest radiation (mantle radiation for lymphoma) has

an

↑risk

of developing breast cancer

Estrogen

treatment

Once

used in hormonal therapy for

prostate cancer treatment

This

treatment may

slightly ↑ BC risk

Concern

that transgender/transsexual individuals who take high doses of estrogens as part of sex reassignment could also have

> BC risk

No studies

of

BC risk

in transgendered individuals, so it isn’t clear what their breast cancer risk

is

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Risk Factors

Obesity

Studies show

women’s BC risk

↑

with postmenopausal

obesity

Obesity also risk

factor for male breast cancer

Fat

cells convert

androgens

into

estrogens

Obese

men have higher levels of estrogens

Testicular Conditions

Undescended testicle

Adult mumps

Uni

/ bilateral orchiectomy

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Pathology

Similar diversity as in women

Lobular male breast cancers previously thought non existence

Because of normally absent terminal lobular unit

Several cases ID for both in situ & invasive lobular cancer

Every histologic entity described in women has occurred in men

In men, mostly ductal type

Most common subtype is invasive papillary cancer

Metastatic patterns similar to women

Lung, adrenal, & bone accounts for most

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Pathology

DCIS distribution in men differs

DCIS 40% mammogram detected cancers in women <50

yo

<5% of all male BC are DCIS

Contralateral BC <2% of men

Inflammatory BC uncommon, but have been described

Superficial dermal

lymphatics

are invaded, leading to edema & vascular congestion

Peau

d’orange

/ hyperemia

Paget’s Disease

Nipple ulceration, bleeding, crust formation w/associated mass

Treatment is analogous to that of invasive ductal cancer

Most male BC are ER+ (87%)

ER+ in men remain constant / independent of age

In contrast, ER+ ↑ with age for women

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Staging

AJCC staging scheme applies identical criteria to both men & women

AJCC

system, effective January 2018, has both clinical &

pathologic staging

systems

Clinical stage

 

Results

of

physical

exam, biopsy,

&

imaging testsUsed

to help plan

treatment

Pathologic

stage

 (also called

surgical

stage

)

Determined

by examining tissue removed during

surgery

T

, N,

&

M

categories

ER

, PR, Her2 status

Grade

of

cancer

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Staging

Comparative review of both 1999-2005, BC in men

Present with larger T

Higher frequency of LN+ (37% vs 22%)

Large median size of nodal

mets

(10 vs 3mm)

Chest wall fixation more common in men

But does not affect prognosis as it does in women

Normal anatomic proximity of breast to skin / muscle accounts for frequency of this finding

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Diagnostic Evaluation

P/e reveals palpable mass

FNA can give diagnosis

Properly obtained specimenAdequate material

Experience

cytopathologist

CNB will provide more information

+/- mammogram for

ipsilateral

or contralateral breast

Subareolar

breast mass with ↑ density / architectural distortion

Calcifications < common, coarser than seen in women

+/- ultrasound

Image-guided core needle biopsy

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Diagnostic Evaluation

Nipple discharge presentation

Collect sample for cytology

DCIS has been described on male nipple ductal secretions

+/-

Ductography

Metastatic work up

For stage II or more advanced disease

Bone scan, LFTs, CT chest, abdomen, pelvis

Identification of

mets

should alter treatment from local to systemic therapy

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Case Presentation

82

yo

Caucasian male of Ashkenazi Jewish descent who presents

with

 

LEFT

palpable mass with aching pain in left side of his

chest x few months.

He

also says that his left nipple has become

inverted

x few

wks

Otherwise

he denies unexplained weight loss, back/bone pain,  abdominal pain, memory/

neuro

deficits.

Does admit to persistent cough.  

RISK FACTORS:

No liver disease, hormone

tx

, prostate issues.

Family history of breast cancer: Yes,  Sister, lumpectomy

79

for breast cancer

Family history of other cancers: Yes,  Father, liver 85.

Smoker: Yes,  Quit 40 years ago. Smoked 1 pack per day 18-28 and 32-35.

Of Ashkenazi Jewish descent

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P/e LEFT central 2 cm breast mass with nipple inversion, no skin changes, no axillary LAD

Mammogram

1.7

cm x 1.7 cm

mass

spiculated

margin

linear calcifications

correlates

as

palpated

nipple retraction

assoc

w/mass

HIGHLY

SUGGESTIVE OF

MALIGNANCY

Ultrasound recommended

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ultrasound

0.5

cm x 1.3 cm x 1.6 cm irregular mass

left

breast central to

nipple

anterior depth is highly suggestive of malignancy.  An

ultrasound

guided biopsy is recommended

.

The 0.9 cm lymph node with focal cortex thickening

left

axilla is

suspicious of malignancy.  An ultrasound guided biopsy is recommended.

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LEFT USG CNB & CNB of axillary LN

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Post biopsy clip

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Ultrasound Guided CNB

LEFT BREAST, RETROAREOLAR, COIL CLIP, ULTRASOUND-GUIDED BIOPSY:

-

INFILTRATING CARCINOMA, DUCTAL TYPE, NOTTINGHAM SCORE 3+2+1=6/9.

- THE TUMOR MAXIMUM LINEAR DIMENSION IS APPROXIMATELY 9 MM.

- THE INFILTRATING CARCINOMA IS ASSOCIATED WITH

CALCIFICATIONS

LEFT

AXILLARY LYMPH NODE, CORE BIOPSY:

- FRAGMENTS OF BENIGN LYMPH NODE.

 

ESTROGEN

RECEPTOR

100

% nuclear staining with strong  intensity      

 

PROGESTERONE

RECEPTOR

100

% nuclear staining with strong  intensity      

 

HER2 EQUIVOCAL

(2+)

FISH

will be performed and results reported in an addendum.              

     

FISH Analysis

HER2 Breast - LEFT BREAST

Results: Negative

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PET scan

FDG

avid soft tissue density nodule

retroareolar

left breast in

keeping

with known neoplasm.

No

PET evidence of FDG avid

adenopathy

or

distant

metastatic disease

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Case Presentation Genetic testing negative

LEFT simple mastectomy & LEFT SLNB

1.7 cm invasive ductal cancer, grade II

No LVI

0/3 negative SLN

Referred to medical oncology

Oncotype

pending

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Surgical Treatment

Major anatomic difference b/w men & women is size of breast & absent breast mound

Leads to differences in local therapy in men

Proportional size of tumor to breast volume is important criteria for selecting of breast conservation

Other major anatomic difference is spatial relationship between the nipple-areola complex (NAC) & breast tissue

Closely related in men, it is often impractical to preserve the NAC

Given the large amount of breast tissue excised & loss of NAC, breast conserving approach is not indicated for most male BC patients

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Surgical Treatment

Psychosocial impact of mastectomy has not been formally addressed in male cohorts

Safe assumption that the breast has a greater value for women in terms of functionality, sexuality, body image, & symmetry

Local therapy for most male BC is mastectomy

NCDB of ACS men (75%) > treated with mastectomy than were women (59%)

LABC should be evaluated for NACT

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Surgical Treatment

Simple mastectomy – removal of breast only

Modified radical mastectomy – removal of breast & axillary LNs

Radical mastectomy for those with

pectoralis

muscle involvement

Breast reconstruction seldom considered in men

Latissimus

flap or TRAM

Axillary staging

Sentinel Lymph Node Biopsy

Axillary Lymph node dissection

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Surgical Treatment

Post

mastectomy closure of the skin defect by

pedicled

latissimus

dorsi

myocutaneous

flap

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Radiation Therapy

Proximity b/w most male BC & skin & chest wall

Extension to or invasion > common than in women

Chest wall involvement in male patients does not portend a different prognosis than that found in patients without involvement

For most, these findings should lead to consideration of radiotherapy

Although no randomized clinical data available

Radiotherapy does ↓ risk LR in men

Extensive or

extracapsular

nodal involvement predictors of regional failure in women

Also apply as criteria for post op XRT in men

NCDB: men more likely to receive

postmastectomy

XRT than women

29% vs 11%, p=0.001

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Systemic Treatment

Stage, age at diagnosis, hormone receptor status

Variables that affect adjuvant systemic therapy

Men have > advanced stage on presentation, ↑ risk of systemic relapse & potential benefits of adjuvant treatment

Also present at later age & therefore have more frequent comorbidities that may limit choices of systemic therapy

Most male BC are ER+, allowing for use of hormone therapy

Which leads to an improvement in survival

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Systemic Therapy

Chemotherapy

L

imited

frequency of use in men (26%) compared to women (40%), p=0.001

But has a role in more aggressive ds providing patient has adequate performance status

Retrospective review 156 male BC at MD Anderson

51 of 135 with

nonmets

BC received either adjuvant chemo, hormonal

tx

, or both

Men with LN+, adjuvant chemo

assoc

w/ lower risk of death (HR 0.78), not stat sig.

OS was

significantly better for men who received adjuvant hormonal therapy (HR 0.45, P=0.01)

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The 21-Gene Recurrence Score Assay (Oncotype DX™) in Estrogen Receptor-Positive Male Breast Cancer: Experience in an Israeli Cohort

Grenader

et al

Oncology 2014;87:1-6

Assess

Recurrence Score

in

Israeli male breast cancer (MBC)

patients

N = 65

RS

assay (

Oncotype

DX™)

performed

on paraffin-embedded tumor samples at Genomic Health

laboratories

Results

Mean

age

65.1

yrs

(38-88

yrs

)

Low-risk

(RS <18), intermediate-risk (RS 18-30)

& high-risk

(RS ≥31) scores were noted in 29 patients (44.6%), 27 patients (41.5%)

&

9 patients (13.9%),

respectively

Distribution

of RS in male patients

similar

to

distribution

in 2,455 female patients from Israel referred during the same time

period

Conclusion

Data

suggest

the

distribution of

Oncotype

DX RS in

ER +

MBC patients is similar

to

female breast cancer

patients

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