Male breast cancer and occult primary

1. UNUSUAL CONDITIONS IN BREAST
CANCER
MALE BREAST CANCER
OCCULT BREAST CANCER
Dr Bharti Devnani
Moderator:- Dr Swarupa Mitra

2. MALE BREAST CANCER

3. EPIDEMIOLOGY
 In the US, app. 2140 new cases of breast cancer in men
are diagnosed annually, and 450 deaths occur; this
represents less than 0.5 percent of all cancer deaths in
men annually.
 By contrast, in Tanzania and areas of central Africa,
breast cancer accounts for up to 6 % of cancers in men.
 In the United States, the ratio of female to male breast
cancer is approximately 100:1 in whites, but lower (70:1)
in blacks.
 Blacks also have a poorer prognosis, even after
adjustment for clinical, demographic, and treatment
factors.

4.  The median age of onset of breast cancer in men is
65 to 67, approximately 5 to 10 years older than in
women
 Race:- Afro caraibbean men (6%)> white men (0.5
%)
(later and more advancerd disease)
 Incidence of breast cancer in men has been
increasing, it has increased 26 %over the past 25
years

5. RISK FACTORS

6. HORMONAL
Testicular abnormalities
 Undescended testes
 Congenital inguinal hernia
 Orchiectomy
 Orchitis
 Infertility
 Mumps affecting testes

7. Klinefelter’s syndrome (XXY )
 Males with Klinefelter’s syndrome have a 50-fold
greater risk of breast cancer over the general
male population.
 KS may be present in 3%–7% of men with breast
cancer.
 The syndrome consists of atrophic testes,
gynecomastia, high serum concentrations of
gonadotropins ( FSH and LH)and low serum
testosterone levels; the net effect is a high ratio of
estrogen-to-testosterone.

8. GENETIC RISK FACTORS
4-16%

9. BRCA-2 mutations
 More common in MBC.(4-16 % mutation carriers)
 Younger age
 Poorer survival
 Highest prevalence in Iceland where founder mutation
is present in 40 % cases.
Other possible mutations
 PALB2
 Androgen receptor
 CYP17
 CHEK2
 PTEN
 hMLH1

10. Family history
 2.5 times greater risk
 15 to 20 percent of men with breast cancer have a
family history of the disease
Prior irradiation
 Chest wall radiation
 Mantle radiation for Hodgkin’s disease

11.  Benign breast disease
 Gynecomastia
 Alcohal use
 Liver disease
 Electromagnetic fields
 Heat
 Volatile organic compounds (e.g.
tetrachloroethylene,perchloroethylene,
trichloroethylene, dichloroethylene, and benzene)

12. •Painless subareolar mass (M C presentation)
•Nipple Retraction, ulceration
•Fixation to skin or underlying muscle
•Nipple involvement is 40 to 50 percent, possibly because of the scarcity of breast
tissue, and the central location of most tumors

13. WORKUP
 Mammogram
(92 % sensitive and 90% specific)
Spiculation,calcification, mass ecentric to nipple.
 USG is a useful adjunct (nodal)
 Biopsy from suspicious mass
 ER, PR and her-2 neu testing
 Metastatic workup(chest imaging , CT abdomen
and bone scan)

14. PATHOLOGIC CHARACTERSTICS
 90 % of breast cancers in men are invasive ductal
carcinomas.
 Lobular cancer :- 1.5 %
The lack of a lobular histologic subtype is due to lack of acini
and lobules in the normal male breast, although these can be
induced in the context of estrogenic stimulation.
 DCIS more common in FBC (20 % v/s 7 to 11% )
 DCIS in men tends to occur at a later age, presents more
frequently in an intraductal papillary form, and is more often
low-grade.
 Paget disease and inflammatory breast cancer are rare.

15. MOLECULAR CHARACTERSTICS
 High rates of hormone receptor (ER/PR) expresssion.
 ER- 90% +
 PR-81% +
 Her-2 neu expression is less likely- 5-15%
Triple negative :- 4%
 Younger patients were more likely to be diagnosed with
a HER2-positive tumor.
 Non-Hispanic black men were more likely to have triple-negative
breast cancer compared to non-Hispanic white
or Hispanic men (9 versus 3 and 6 percent,respectively).

16. DIFFERENTIAL DIAGNOSIS
 Gynecomastia
 Breast abscess
 Metastases to the breast
 Sarcomas

17. DIFFERENCES FROM FEMALE CANCER
 Average age of presentation is late (5-10 yrs).
 Presents in more advanced stages with retroareolar
location and chest wall involvment.
 BRCA-2 > >BRCA-1
 Lobular histologies uncommon (15 % v/s 1.5%)
 High rates of hormone receptor expression

18. SURGERY
 MRM + ALND is standard approch.
 Extensive chest wall muscle involvment :- Radical
mastectomy
 BCS less appropriate
 Presentation in more advanced stage
 Retroareolar & chest wall inv
 Scarcity of breast tissue
 SLN :- data is limited but feasible.
ASCO expert -acceptable

19. Reconstructive surgery
 40% - stage III /IV
 Extensive resection, skin closure difficult
 Goal is adequate skin coverage in comparison to
volume replacement in FBC

20. HORMONAL THERAPY
 High expression of ER/ PR receptor
 Tamoxifen for 5 years recommended
 Based largely upon the benefits that have been observed in
clinical trials performed in women
 Paucity of Prospective trials to confirm the validity of this
approach in men.
 Retrospective comparisons support a survival benefit from
adjuvant tamoxifen in MBC (61 versus 44 percent) and disease-free
survival (56 versus 28 percent) compared with a group of
historical controls who underwent mastectomy alone
 Low adherence:- VTE, Decrease libido, hot flushes,wt gain,
social support

21. Aromatase inhibitors
 There are insufficient data to support the use of an AI in
the adjuvant setting for breast cancers in men.
 Unable to prevent testes derived estrogen synthesis
which is the source of 20% of endogeneous estrogen in
men.
 The recommended choice is tamoxifen rather than an
AI in the adjuvant setting for men with breast cancer.
 Her-2 – Transtuzumab
 Insufficient data

22. CHEMOTHERAPY
 Chemo less frequently used than FBC
 Hormone unresponsive tumors (ER-)
 Retrospective studies revealed NS trend in men
with node + disease toward better outcome

23. METASTATIC DISEASE
 Hormonal manipulation :- Ist line therapy
 Origionally performed surgically via orchidectomy,
adrenalectomy or hypophsectomy.(morbid)
 Tamoxifen:- as effective as Sx
 AI :- shown benefit in metastatic setting
AI+ orchidectomy Complete estro supp.
AI+ LHRH analogues
Hormone refrectory :- chemo

24. CONTRALATERAL BREAST CANCER
 The risk of a C/L breast cancer appears to be higher for men than it is
FBC.
 Compared to the general population, the standardized incidence ratio
(SIR) for C/L breast cancer in male survivors was 30. However, for
men diagnosed < 50 yrs the SIR was 110.
 Men with a h/o breast cancer had a 93-fold higher risk of developing
c/l breast cancer than men without such a history.
 The absolute risk for an individual man with breast cancer developing
a c/l breast cancer was 1.75 %
 Despite the significantly increased risk of a c/l cancer in men with a
h/o breast cancer, the absolute risk of a c/l breast cancer is much
greater in women because of the higher prevalence of the disease.
 The role of screening mammography for the c/l breast in men with
MBC has not been explored.

25. SURVIVORSHIP ISSUES
 ¼ discontinue T/t
 Socially isolating for men, stigmatized by their
diagnosis.
 Greater adjustment diff
 Poor physical and mental health
 Late age presentation :- more CV risks.

26. OCCULT BREAST CANCER

27.  Cancer of unknown primary site (CUP), defined as the
presence of metastatic cancer with an undetectable
primary site at the time of presentation.
 2 % of all cancer diagnoses.
 Occult breast cancer (OBC), which manifests as an
axillary lymph node metastasis without a detectable
primary breast tumor on clinical examination or
radiography, is a rare presentation.
 OBC accounts for 0.3-1% of all breast cancers.

28.  Occult primary breast cancer was first recognized
by William Halsted, who described three patients
presenting with axillary masses that were
eventually found to represent breast cancer.
 In modern series, occult breast cancer accounts for
0.1 to 0.8 percent of all newly diagnosed breast
cancers and the incidence has not decreased with
improvements in breast imaging

30. DIAGNOSTIC WORK-UP
 The first step in the diagnostic workup of a patient
with unexplained axillary adenopathy is a biopsy.
 Besides standard light microscopic examination of
H & E stained sections, other techniques such as
IHC and sometimes electron microscopy can help
to narrow the differential diagnosis.

31. Histologies
 70 % are adenocarcinomas
 15 to 20 % are poorly differentiated carcinomas
 10 % represent poorly differentiated
adenocarcinomas.
 The remainder are squamous cell, neuroendocrine,
or poorly differentiated neoplasms.

32. DIFFERENTIAL DIAGNOSIS
 Lymphomas
 Melanomas
 Sarcomas
 Thyroid cancers
 Skin cancers
 Lung cancers
 Less often, uterine, ovarian, sweat gland, or gastric
cancers.
In approximately 30 percent of cases, the primary
site is never identified

33. IHC MARKERS
 CEA
 CK- 7 and CK-20
 ER/PR
 Gross cystic disease fluid protein-15 (GCDFP)
 Mammaglobin
 Thyroid transcription factor (TTF-1)
 CA-125
 In men :- Markers for prostste cancer

38. Advantages of MRI
 Breast MRI is more sensitive.
 Breast MRI can detect a primary breast cancer in
approximately 75 % of women who present with ALN mets
with negative clinical exam & imaging.
 Identification of a primary breast cancer by MRI may
facilitate BCS instead of mastectomy.
 Some lesions found on MRI can be identified on
subsequent, targeted "second-look” ultrasound and may
then be biopsied under US guidance.
Disadvantages
 High false positive results. (29 %)
 All suspicious findings on MRI require pathologic
confirmation.

39. OBC
ALND
alone
MRM+
ALND
ALND +
XRT

40. LRFS
RFS
BCSS

42.  Patients with OBC who present with axillary lymph
node metastasis should receive the standard
treatment.
 No differences in outcomes were observed
between patients who received ALND followed by
subsequent breast radiotherapy and patients who
underwent mastectomy plus ALND.

43. MANAGMENT
Local treatment for breast is necessary in conjunction with ALND.
Mastectomy —
 A standard approach is to perform a modified radical mastectomy
(MRM) at the time of ALND.
 A breast malignancy will be found upon histologic review of the
mastectomy specimen in approximately 65 percent of patients.
ALND + XRT
 Observation alone is deterimental.

44.  Radiation — The role of WBI as a breast-conserving
alternative to mastectomy is unclear.
 No RCT comparing MRM + ALND to WBI + ALND.
 Only available data are from small retrospective case
series.
Local
control
73-100%

45. PROGNOSIS

46. SUMMARY OF TREATMENT
 All patients should undergo ALND
 Optimal treatment for the ipsilateral breast is controversial. Standard
approach is to perform MRM at the time of ALND.
 For women who wish to preserve their breast, WBI is an acceptable
option.
 Observation alone for the ipsilateral breast is not recommended.
 Systemic adjuvant therapy according to published guidelines for stage
II primary breast cancer is recommended.
 Women with ALN mets who have adenoca or poorly differentiated
carcinoma histology, compatible IHC staining, and no evidence of a
breast cancer primary but who have evidence of other distant
metastases should be treated according to guidelines for metastatic
breast cancer

47. THANK YOU