UNUSUAL CONDITIONS IN BREAST CANCERMALE BREAST CANCEROCCULT BREAST CANCER

Dr Bharti Devnani

Moderator:- Dr Swarupa Mitra

MALE BREAST CANCER

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.

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

RISK FACTORS

HORMONAL

Testicular abnormalities Undescended testes Congenital inguinal hernia Orchiectomy Orchitis Infertility Mumps affecting testes

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.

GENETIC RISK FACTORS

4-16%

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

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

Benign breast disease Gynecomastia Alcohal use Liver disease Electromagnetic fields Heat Volatile organic compounds (e.g.

tetrachloroethylene,perchloroethylene, trichloroethylene, dichloroethylene, and benzene)

•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

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)

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.

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).

DIFFERENTIAL DIAGNOSIS

Gynecomastia Breast abscess Metastases to the breast Sarcomas

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

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

Reconstructive surgery 40% - stage III /IV Extensive resection, skin closure difficult Goal is adequate skin coverage in

comparison to volume replacement in FBC

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

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

CHEMOTHERAPY

Chemo less frequently used than FBC

Hormone unresponsive tumors (ER-) Retrospective studies revealed NS trend in

men with node + disease toward better outcome

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 settingAI+ orchidectomy Complete estro supp.AI+ LHRH analogues

Hormone refrectory :- chemo

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.

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.

OCCULT BREAST CANCER

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.

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

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.

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.

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

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

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.

OBC

ALND alone

MRM+ALND

ALND + XRT

LRFS

RFS

BCSS

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.

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.

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%

PROGNOSIS

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

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