BREAST CA

DONE BY DUA’A SUMA’AN

6th y medical student Supervised by DR Rami Yagan

Surgery rotation /KAUH29/9/2015

Objects

• Histological classification of malignant breast ca

• Phyllodes tumor • Significance of estrogen receptor positivity• Significance of HER2 mutation positivity

Anatomy

• Lobule ( 10-100) ductule Lactiferous duct ( 15-20) ampulla nipple

HistologyThe breast composed mainly of :ducts and lobules ; lined by epithelium , imbedded in fibrous stroma ; connective tissue , mesenchymal origin with fat cells .

Histological classification of breast cancer• 1. Epithelial tumors Ductal Ductal carcinoma in situ (DCIS) Invasive ductal carcinoma

(IDC) Inflammatory breast

carcinoma Paget’s disease

Lobular Lobular carcinoma in situ (LCIS) Invasive lobular carcinoma

(ILC)

• 2. Stromal or mesenchymal tumors

Sarcoma• 3. Biphasic tumors Phylloides Fibroadenoam• 4. Others Lymphoma Secondary metastasis

Epithelial tumors95% are ductal ( arise from the ducts ) 5% are lobular ( arise from lobules).

If the tumor cells invade the basement membrane it is called invasive or infiltrative , we have • Invasive ductal carcinoma (IDC)• Invasive lobular carcinoma (ILC )

If the tumor cells don’t show invasion beyond the basement membrane , its called In situ , we have • Ductal carcinoma in situ (DCIS)• Lobular carcinoma in situ (LCIS)

• Breast cancer can produce what is called dysmoplastic reaction , which is the formation of fibrosis around the tumor as if the body is trying to confine the tumor , so most of the bulk of breast tumor will actually be a fibrous tissue

DCIS

• usually occurs in localized areas of breast , but may be extensive , if untreated will become invasive .

• Generally asymptomatic , appear as mammogram finding , sometimes with microcalcification .

• Because of its malignant potential , treatment is complex excision of the disease , and extensive disease ( >or = 4 ) may necessitate mastectomy

LCIS• It is a marker of increased risk of breast cancer

(approximately 20% over 20 year period)• An incidental finding of LCIS on diagnostic

biopsy requires no surgery .• However when LCIS is found on core biopsy of

an area of mammographic calcification , it may be associated with invasive lobular carcinoma and therefore formal diagnostic excision biopsy should be considered

Invasive lobular carcinoma

• Around 10%• The most common between the age 45-55• It does not always form a firm lump but rather

an area of thickening , so tend to present late .

IDCInvasive ductal carcinoma

IDC not otherwise

specified (NOS )

Less common forms of IDC :

Is the commonest type Is called scirrhous

carcinoma of the breast because it contains fibrous tissue due to extensive dysmoplastic reaction .

• tubular• medullary• cribriform •mucinous

IDC is the most common type 85%

Inflammatory breast cancerMost malignant form of breast ca , Poor prognosis .

Constitute < 3% of all cases .

One variant of ductal carcinoma

The clinical findings consist of rapidly growing , Present as a picture of inflammation (mastitis or cellulitis ) with erythema , pain , hotness & edema .

Usually there’s no palpable mass because the skin is thick & edematous .

Orange peel appearance or peau d’orange appearance; are caused by carcinomatous invasion of subdermal lymphatics , with resulting edema and hyperemia . Appear as pitted skin at the site of hair follicles.

• If the practitioner suspect infection but the lesion not respond rapidly (1-2 weeks) to antibiotics , biopsy should performed .

• The diagnosis should be made when the redness involves more than 1/3 of the skin over the breast and biopsy shows infiltrating carcinoma with invasion of subdermal lymphatic’s .

• Metastases tend to occur early and widely , and for this reason , inflammatory carcinoma is rarely curable .

• Radiation, hormone therapy, and chemotherapy are measure most of value rather than operation .

• Mastectomy is indicated when chemotherapy and radiation have resulted in clinical remission with no eveidence of distant metastases . In these cases , residual disease in the breast may be eradicated .

Paget’s disease of the nippleRare malignant condition - 1%It affects the nipple and may or

may not be associated with breast mass .

The 1st symptom is often itching or burning of the nipple, with superficial erosion or ulceration .

Chronic skin changes involving the nipple of the breast such as dry scaling or red weeping.

The basic lesion is usually a well differentiated infiltrating ductal carcinoma or a DICS .

Should be differentiated from eczema , which involves the areola with little involvement of the nipple.

The diagnosis is established by biopsy of the area of erosion.

Mesenchymal breast cancers

• “ sarcomas” big in size .• V. rare 0.5 %• Any mesenchymal cell in the breast can retain

its progenesety and produce any type of mesenchymal cancers .

• E.g; osteosarcoma in the breast or vascular sarcomas ..

Biphasic breast tumorsInvolving more than one type of tissue in

these tumors .Include :

Fibroadenoma : ( commonest benign tumor) Involve both epithelial and stromal cells Phyllodes : fibroepithelial tumors composed of an epithelial and a cellular stromal component .

phyllodes• FIBROADENOMA LIKE TUMOR with cellular stroma that grows

rapidly . “cystosarcoma phyllodes”

• The name "phyllodes," which is taken from the Greek language and means "leaflike," refers to that fact that the tumor cells grow in a leaflike pattern

• Around 40’s• The lesion can be benign or malignant , usually benign ( 10% frank

benign , 10% frank malignant & 80% intermediate )

• It may reach a large size , and if inadequately excised , will recur locally .

• It has a smooth, sharply demarcated texture and typically is freely movable.

• It is a relatively large tumor, with an average size of 5cm. However, lesions of more than 30cm have been reported.

• The etiology of phyllodes tumors is unknown

• If benign , phyllodes tumor is treated by local excision with a margin of surrounding breast tissue .

• The treatment of malignant phyllodes tumor is more controversial , but complete removal of the tumor with a rim of normal tissue avoids recurrence .

• Because these can be large , simple mastectomy is sometimes necessary

• L.N dissection is not performed , since sarcomatous portion of the tumor metastasizes to the lung .

Micrograph of a phyllodes tumor (right of image)

with the characteristic long clefts and myxoid cellular stroma. Normal

breast and fibrocystic

change are also seen (left of image). H&E

stain

Phyllodes tumor in mammography

Biomarker • The ER &PG status and HER-2/neu status of the

tumor should be determined at the time of initial biopsy .

• These markers may be obtained on core biopsy specimens, which will be necessary to institute neo-adjovant therapy .

• The presence or absence of ER and PR is a critical element of breast cancer management.

• Pt whose primary tumors are receptor + have more favorable coarse than those receptor - .

• Estrogen receptors (ERs) , Progesterone receptors (PgRs) are exepressed on the surface of tumor cells in breast ca .

• Up to 60% of patients with metastatic breast ca will respond to hormonal manipulation if ER receptor + . Fewer than 5% of pt with metastatic , ER – tumors can be treated .

• Hormone receptors have no relationship to response to chemotherapy .

Hormons & growth factors receptors

Cancers are divided into:

1.hormone sensitive (ERS+ , PgRs +)Which benefit from anti estrogen therapy such as

tamoxifen , raloxifen or aromatase inhibitor

2.Hormone resistant (ERs - , PgRs -) : no benefit from hormone therapy , so poor prognosis

Estrogen receptors:

• The female hormone estrogen can play a part in stimulating some breast cancers to grow.

• If your breast cancer has receptors within the cell that bind to estrogen it is known as estrogen receptor positive or ER+ breast cancer.

• All breast cancers are tested for estrogen receptors using tissue from a biopsy or after surgery, and your pathology report will state if there are any ER+ cells. Some reports will also comment on whether there are progesterone receptor positive (PR+) cells.

• If you have invasive breast cancer which is estrogen receptor positive you will usually be advised to have hormone (endocrine) therapy.

• Hormone therapy is much less commonly used with ductal carcinoma in situ (DCIS) because the benefits are less certain.

• If your breast cancer is hormone receptor negative, hormone therapy drugs will not be of any benefit to you.

• Tumors that are ER/PR-positive are much more likely to respond to hormone therapy than tumors that are ER/PR-negative.

• You may have hormone therapy after surgery, chemotherapy, and radiation are finished. These treatments can help prevent a return of the disease by blocking the effects of estrogen. They do this in one of several ways.

• The medication tamoxifen (Nolvadex) helps stop cancer from coming back by blocking hormone receptors, preventing hormones from binding to them. It’s sometimes taken for up to 5 years after initial treatment for breast cancer.

• A class of medicines called aromatase inhibitors actually stops estrogen production. These include anastrozole (Arimidex), exemestane (Aromasin), and letrozole (Femara). They’re only used in women who’ve already gone through menopause

HER2 testing: • Human epidermal growth factor receptor

• All invasive breast cancers are tested for HER2 levels. • 25% of breast ca are HER 2 + ( overexpressed)• It’s done in a hospital laboratory on a sample of breast cancer tissue removed

during a biopsy or surgery. The results are usually available one to three weeks later.

• Outside of a clinical trial , HER2 testing is normally only done on invasive breast cancer, so this is unlikely to be mentioned if you have ductal carcinoma in situ (DCIS).

• The following are the three most commonly used ways to measure HER2 levels.- IHC (immunohistochemistry) is usually done first. It’s reported as a score

ranging from 0–3. - A score of 0 or 1+ is means the breast cancer is HER2 negative.- A score of 2+ is borderline, - a score of 3+ means the breast cancer is HER2 positive. - The other ways of measuring HER2 are called FISH (fluorescent in situ

hybridisation) and CISH (chromogenic in situ hybridisation).

• People with HER2 positive invasive breast cancer are likely to be advised to have chemotherapy and also drug treatments called targeted therapies.

• These drugs work by blocking specific ways that breast cancer cells divide and grow.

• The most well-known targeted therapy istrastuzumab (Herceptin). Trastuzumab works by attaching itself to the HER2 proteins (also known as receptors) so that the cancer cells are no longer stimulated to grow.

• It also helps the body’s immune system destroy breast cancer cells.

• Only people whose cancer is HER2+ will benefit from having trastuzumab.

• Another drug, lapatinib (Tykerb), is often given if trastuzumab doesn’t help. Ado-trastuzumab emtansine (Kadcyla) can be given after trastuzumab and a class of chemotherapy drugs called taxanes, which are commonly used to treat breast cancer.

• Pertuzumab (Perjeta) can be used with trastuzumab and other chemotherapy medicines to treat advanced breast cancer. This combination can also be given before surgery to treat early breast cancer. In one study, the combination of the two drugs it was shown to extend life

The most important growth factor group is human epidermal growth factor receptors known as HER. We have 4 subtypes , most important is HER 2

which is +ve in 20% of cases of breast ca Cancer cells express more number of HER 2

receptors on their surface , so more uncontrolled growth.

Monoclonal AB block HER2 receptors called herceptin or trastuzumab cause growth reduction & shrinkage of tumor cells.

All breast cancers should be checked for Ers and HER2.

Triple-Negative Breast Cancer

• Some breast cancers -- between 10% and 20% -- are known as “triple negative” because they don’t have estrogen and progesterone receptors and don’t overexpress the HER2 protein. Most breast cancers associated with the gene BRCA1 are triple negative.

• These cancers generally respond well to chemotherapy given after surgery. But the cancer tends to come back. So far, no targeted therapies have been developed to help prevent cancer returning in women with triple-negative breast cancer. Cancer experts are studying several promising strategies aimed at triple-negative breast cancer

Thank yu