1. (Handling and Evaluation of Breast Cancer Biopsy)
بسم الله الرحمن الرحيم
Lab 7
(Handling and Evaluation of Breast Cancer Biopsy)

2. What is cancer?
Cancer is a group of diseases characterized by unregulated cell growth and the invasion and spread of cells from the site of origin, or primary site, to other sites in the body.
Cancer starts when cells begin to grow out of control.
Cells in nearly any part of the body can become cancer, and can spread to other areas of the body.

4. Breast cancer
is a disease in which malignant (cancer) cells form in the tissues of the breast.
is a heterogeneous disease with varied morphological appearances, molecular features, behavior, and response to therapy.

6. Types of breast cancers
Most breast cancers are carcinomas, a type of cancer that starts in the cells (epithelial cells) that line organs and tissues like the breast.

7. Other types of cancers can occur in the breast, too, such as sarcomas, which start in the cells of muscle, fat, or connective tissue.

8. Is breast cancer invasive?
If breast cancer is found, it’s important to know whether the cancer has spread outside the milk ducts or lobules of the breast where it started.
Non-invasive cancers stay within the milk ducts or milk lobules in the breast. They do not grow into or invade normal tissues within or beyond the breast.
Non-invasive cancers are sometimes called in situ or pre- cancers.

9. If the cancer has grown into normal tissues, it is called invasive
If the cancer has grown into normal tissues, it is called invasive. (Most breast cancers are invasive).
Sometimes cancer cells spread to other parts of the body through the blood or lymph system.
When cancer cells spread to other parts of the body, it is called metastatic breast cancer.
In some cases, a breast cancer may be both invasive and non-invasive.

11. One of the best-established prognostic factors in breast cancer is histological grade, which represents the morphological assessment of tumor biological characteristics and has been shown to be able to generate important information related to the clinical behavior of breast cancers.

13. The three main prognostic determinants used in routine practice to determine the breast cancer stage and for treatment:
lymph node (LN) status,
tumor size
Histological grade.
Receptor (ER,PR,HER).

14. The introduction of high-throughput technologies that survey thousands of genes and their products in a single assay, coupled with powerful analytical tools, has opened up new avenues for classifying breast cancer into biologically and clinically distinct groups based on gene expression patterns and DNA copy number alterations.

15. To evaluate the histological tumor grade hematoxylin- eosin-stained tumor tissue sections are prepared by an appropriately trained pathologist using a standard protocol.
Histology Grade based on the evaluation of three morphological features:
degree of tubule or gland formation,
nuclear pleomorphism,
mitotic count.

17. There are four types of biopsy used to check for breast cancer:
Excisional biopsy : The removal of an entire lump of tissue.
Incisional biopsy : The removal of part of a lump or a sample of tissue.
Core biopsy : The removal of tissue using a wide needle.
Fine-needle aspiration (FNA) biopsy : The removal of tissue or fluid, using a thin needle.

18. Immunohistochemistry for the assessment of ER/PR, HER2 expression in breast cancer
Immunohistochemistry (IHC) is used to define four breast cancer subtypes for expression of estrogen receptor (ER) or progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2):
ER/PR+, Her2+
ER/PR+, Her2− (most common)
ER/PR−, Her2+
ER/PR−, Her2−.
The assessment of HER2 in human tumor cells has recently become important since the amplified gene is predictive of response to the novel humanized HER2 antibody Herceptin®/trastuzumab.
Historically the major factors directing the appropriate treatment for breast cancer have been those regarding prognosis, such as indicators of how long the average patient is likely to survive. As a result, the relative aggressiveness of a tumor has been gauged and the appropriate treatment regime has been planned.
HER2 is a member of the epidermal growth factor receptor (EGFR) family of molecules and is encoded for by the HER2 proto-oncogene on the long arm of chromosome 17. HER2 is overexpressed in 10–20% of primary breast cancers. Overexpression indicates poor prognosis. Breast cancers showing over expression are candidates for treatment with trastuzumab (Herceptin). Studies show that trastuzumab can reduce the risk of occurrence by one-half and mortality by one-third in early-stage breast cancer patients.

19. About 80% of all breast cancers are “ER-positive
About 80% of all breast cancers are “ER-positive.” That means the cancer cells grow in response to the hormone estrogen.
About 65% of these are also “PR-positive.” They grow in response to another hormone, progesterone.
The triple negative subtype (TNBCs) are called such because they lack receptors for estrogen, progesterone and Her2. (ER/PR−, Her2−) had the worst overall survival. 
Tumors that are ER/PR-positive are much more likely to respond to hormone therapy than tumors that are ER/PR-negative.

20. You may have hormone therapy after surgery, chemotherapy, and radiation are finished.
These medications  taken help stop cancer from coming back by blocking hormone receptors.
A class of medicines called aromatase inhibitors actually stops estrogen production. They’re only used in women who’ve already gone through menopause.

21. The same line of therapy however had little or no effect on patients with estrogen receptor negative (ER-) breast cancer.
Another important progress in breast cancer therapy was identifying and targeting the Her2 subtype of epidermal growth factor receptors (EGFR) which improved the outcome of Her2 positive patients.

22. HER-2
In about 20% of breast cancers, the cells make too much of a protein known as HER2. These cancers tend to be aggressive and fast-growing.
The standard of care to treat curable HER2-positive breast cancer has been to give chemotherapy with the HER2-targeted monoclonal antibody.
Formalin-fixed paraffin sections immunostained to demonstrate HER2 are examined microscopically and scored.

23. It is recommended that formalin-fixed paraffin sections should be antigen retrieved using the water bath method and citrate buffer, pH 6.0, to ensure optimal immunostaining.

24. Types of treatment:
1. Surgery is the primary method of treatment and few patients elect to bypass this option as it is considered necessary to stop cancer progression. 2. Radiation therapy is the next step, which uses x-rays and other radioactive materials to damage DNA and cell membranes of cancer cells. 3. Chemotherapy is the third step, which is the use of chemical agents that destroy dividing cells or stop their division. One of the most popularly used chemotherapeutic agents is cisplatin, which in general is a systemic treatment.

25. Any breast abnormality is a cancer?
A lump or spot in the breast can be made of normal cells or cancer cells which may stay in the place where they started to grow, or they may grow into the normal tissue around them.
Cancer cells may also spread beyond the breast.
The abnormal lump or spot may be found using mammography or other testing methods.
A procedure called a biopsy removes a piece of tissue from the lump or spot to find out if cancer cells are present.

26. Inflammatory Breast Cancer
It is a rare (accounting for 1 to 5 percent of all breast cancers diagnosed in the United States).
and very aggressive disease in which cancer cells block lymph vessels in the skin of the breast.
This type of breast cancer is called “inflammatory” because the breast often looks swollen and red, or inflamed.

27. Most inflammatory breast cancers are invasive ductal carcinomas, which means they developed from cells that line the milk ducts of the breast and then spread beyond the ducts.
Compared with other types of breast cancer, inflammatory breast cancer tends to be diagnosed at younger ages.
Inflammatory breast tumors are frequently hormone receptor negative, which means they cannot be treated with hormone therapies, such as tamoxifen, that interfere with the growth of cancer cells fueled by estrogen.

28. Benign breast conditions

29. Thanks a lot