Types & Sub-types of Breast Cancer

Various types & sub-types of breast cancer, Source of origin, Breast anatomy, Breast biopsy sample analysis, Estrogen positive breast cancer, Progesterone positive breast cancer, HER2 positive breast cancer, Triple negative breast cancer,

1. Cancer Research TYPES & SUB-TYPES OF BREAST CANCER

2. TYPES & SUB-TYPES OF BREAST CANCER Mr. Shaktiprasad Pradhan M.Pharm, Ph.D* Research Professional, UDPS [email protected] Utkal University, Bhubaneswar Odisha, India

3. . INTRODUCTION 3

4. The Breast The human female breast is an apocrine gland having remarkable and complex structure. Most part of a woman's breast consists of fat & connective tissue, along with less conspicuous parts including milk ducts, lobes, lobules, arteries and lymph nodes. Each breast has 15 to 20 lobes (sections) & each lobe is made up of many lobules (smaller structures) that end in tiny bulbs that can produce milk. Lobes, lobules & bulbs are linked by a network of thin tubes, known as ducts . Ducts carry milk from the bulbs, where it's produced, toward the areola (dark area of skin in the center of the breast). (Cont.) 4

5. . They join together into larger ducts ending at the nipple , where milk becomes available to a hungry infant. The actual milk producing structures are nearly the same in all women. Space around the lobules and ducts are filled with fatty tissue, ligaments and connective tissue. Breast has no muscle tissue, but muscles do lie underneath the breasts, separating them from ribs. Oxygen, nutrients & other life sustaining nourishments are delivered to breast tissues by the blood in arteries and capillaries. 5

6. Anatomy of a Female Breast 6 1. Chest wall 2. Pectoralis muscles 3. Lobules 4. Nipple surface 5. Areola 6. Lactiferous duct tube 7. Fatty tissue 8. Skin.

7. . BREAST CANCER 7

8. Breast Cancer Breast cancer is a type of cancer that develops from the breast cells, usually starts in the inner lining of milk ducts or the lobules that supply them with milk. It occurs in both males and females but the vast majority of breast cancer cases occur in females. It accounts for 16% of all female cancers, 22.9% of invasive cancers in women & 18.2% of all cancer deaths (both males & females from breast cancer) globally. Breast cancer is more common in elderly women & the rate is much higher in developed countries in compared to the developing ones. The different lifestyles and eating habits contributes a lot for the occurrence of breast cancer. However breast cancer is the most detectable & most treatable type of cancer among all human malignancies. 8

9. . ORIGIN SITES OF BREAST CANCER 9

10. Origen Sites of Breast Cancer The type of tissue where the breast cancer arises determines how the cancer behaves and what treatments are most effective. Usually the parts of the breast where cancer origins, include: Milk ducts Ductal carcinoma is the most common type of breast cancer. Ductal carcinoma can remain within the ducts as a non-invasive cancer (ductal carcinoma in situ) or it can break out of the ducts (invasive ductal carcinoma). Milk producing lobules Lobular carcinoma starts in the lobules of the breast, where breast milk is produced. (Cont.) 10

11. . When it breaks out of the lobules, it's considered invasive lobular carcinoma. Connective tissues Rarely breast cancer can begin in the connective tissue that's made up of muscles, fat and blood vessels. Cancer that begins in the connective tissue is called sarcoma. Examples of sarcomas that can occur in the breast include phyllodes tumor and angiosarcoma. The type of tissue where the cancer arises in the breast determines the type of the breast cancer and accordingly most effective treatments are preferred. 11

12. . Origin Sites of Breast Cancer 12

13. . BREAST BIOPSY SAMPLE ANALYSIS 13

14. Breast Biopsy Sample Analysis Pathological microscopic examinations of a breast tumor tissue, from biopsy samples are performed for: Unique appearances as Some subtypes of breast cancer are named after how they appear under the microscope including tubular, mucinous, medullary and papillary. The subtype gives suggestion regarding prognosis and how the breast cancer cells may respond to treatment. Cancer grade or Degree of difference between the cancer cells and normal cells as The difference in looking of cancer cells from normal cells is called cancer's grade. (Cont.) 14

15. . Breast cancers are graded on a 1 to 3 scale, with grade 3 cancers being the most different looking and considered the most aggressive type, so accordingly the treatment is preferred. A sample of breast cancer tissue from a biopsy procedure may be tested for analyzing the genetic makeup of breast cancer as this might be helpful in the management or treatment of breast cancer. HER2  gene. Cancer cells that have too many copies of the  HER2  gene (HER2-positive cancers) produce too much of the growth promoting protein called HER2. Targeted therapy drugs are available to shut down the HER2 protein, thus slowing the growth and killing these cancer cells. (Cont.) 15

16. . Other tumor markers . This information can be used to interpret the genetic makeup of tumor cells, so by knowing the tumour markers the need of aggressive treatments can be decided. For example, women with relatively low risk of breast cancer (fewer markers) may avoid aggressive treatments. Genetic information about breast cancer cells are increasingly used to categorize breast cancers in different groups , which ultimately helps to choose the most effective treatment for the specific type of breast cancer. Group 1 (Luminal A):  This group includes tumors that are ER positive and PR positive , but negative for HER2 . Likely to be benefitted from hormone therapy and chemotherapy. (Cont.) 16

17. . Group 2 (Luminal B):  This group includes tumors that are ER positive, PR negative and HER2 positive. Likely to be benefitted from chemotherapy and hormone therapy and the treatment targeted to HER2. Group 3 (HER2 positive):  This group includes tumors that are ER negative and PR negative, but HER2 positive . HER2 breast cancers are likely to be benefitted from chemotherapy and treatment targeted to HER2. Group 4 (Basal like):  This group, which is also called triple-negative breast cancer, includes tumors that are ER negative, PR negative and HER2 negative. Basal like breast cancers are likely to be benefitted from chemotherapy. 17

18. . TYPES OF BREAST CANCER 18

19. Types of Breast Cancer Basically breast cancers are of 2 different types as Non-invasive breast cancer & Invasive breast cancer. Non-invasive breast cancer: (2 types) Cancer that are contained within the milk ducts or lobules in the breast. They have not grown into or invaded, the normal breast tissue. Non-invasive cancers are called carcinoma in situ and are sometimes referred to as pre cancers. These are of 2 types as Ductal carcinoma in situ (DCIS) Lobular carcinoma in situ (LCIS) (Cont.) 19

20. . Ductal carcinoma in situ (DCIS) DCIS is the most common type of non-invasive breast cancer. It starts in the milk ducts of the breast and is non-invasive because it hasn't spread into any surrounding breast tissue. DCIS isn't life threatening , but having DCIS can increase the risk of developing an invasive breast cancer later in life.  Lobular carcinoma in situ (LCIS) LCIS is non-invasive breast cancer that grows in the lobules (the milk-producing glands at the end of breast ducts). It is non-invasive as it has not spread into any surrounding breast tissue. LCIS isn't life threatening , but having LCIS can increase the risk of developing invasive breast cancer later on in life. (Cont.) 20

21. 21 Ductal Carcinoma In S itu (DCIS)

22. 22 Lobular Carcinoma In S itu (LCIS) Breast A: Ducts, B:Lobules, C: Dilated section of duct to hold milk, D: Nipple, E: Fat, F: Pectoralis major muscle, G: Chest wall Enlarged Lobule A: Normal lobular cells, B: Lobular cancer cells, C: Basement membrane.

23. . Invasive breast cancers: (7 types) Breast cancers that have spread outside the ducts or lobules of the breast into surrounding breast tissue. Early breast cancer  is the term that refers to cancer that is contained within the breast and may have spread to surrounding lymph nodes in the breast or armpit (axilla) but not anywhere else in the body. Type-1, Invasive ductal carcinoma (IDC): IDC is the most common type of breast cancer about 80% of all the breast cancers. Invasive ductal carcinoma means that the cancer that began in the milk ducts of the breast has broken through the lining of the milk duct and spread into the surrounding breast tissue. (Cont.) 23

24. 24 Invasive ductal carcinoma (IDC) Breast A: Ducts, B:Lobules, C: Dilated section of duct to hold milk, D: Nipple, E: Fat, F: Pectoralis major muscle, G: Chest wall Enlarged Cell A: Normal duct cells, B: Ductal cancer cells breaking through the basement membrane, C: Basement membrane.

25. . Over time invasive ductal breast cancer can spread to the lymph nodes and potentially to other parts of the body. Type-2, Invasive lobular carcinoma (ILC): ILC is the second most common type of breast cancer after invasive ductal carcinoma. Invasive lobular carcinoma means that the cancer that began in the milk producing lobules of the breast has broken through the lining of the lobule and spread into surrounding breast tissue. Over time invasive lobular breast cancer can spread to the lymph nodes and potentially to other parts of the body. (Cont.) 25

26. 26 Invasive lobular c arcinoma (ILC) Breast A: Ducts, B:Lobules, C: Dilated section of duct to hold milk, D: Nipple, E: Fat, F: Pectoralis major muscle, G: Chest wall Enlarged Lobule A: Normal lobular cell, B: Lobular cancer cells breaking through the basement membrane, C: Basement membrane

27. . Type-3, Paget’s disease (PD): Paget's disease of the nipple is a rare form of breast cancer in which cancer cells grow in the nipple or the areola (the area around the nipple). The nipple and areola often become scaly, red, itchy and irritated. Many people with Paget’s disease also have either DCIS or invasive breast cancer somewhere else in the breast. The unusual changes in the nipple and areola are often the first signs, that breast cancer is present. Type-4, Inflammatory breast cancer (IBC): IBC is a rare and aggressive form of invasive breast cancer that affects the blood vessels in the skin and/or lymphatic vessels of the breast. (Cont.) This causes the breast to become red and inflamed. 27

28. . Type-5, Phyllodes tumour (PT): Phyllodes tumours of the breast are rare, although most phyllodes tumours are benign (not cancerous) and some are malignant (cancerous). Phyllodes tumours tend to grow quickly, but they rarely spread outside the breast. Phyllodes tumours develop in the breast’s connective tissue or stroma (the tissue that holds everything together inside the breast) i.e. outside the ducts and lobules of the breast.  Type-6, Locally advanced breast cancer (LABC): LABC is an invasive breast cancer that is large or has spread beyond the breast to other nearby areas such as the skin, chest wall or muscle and may have extensive local lymph node involvement.   (Cont.) 28

29. 29 Type-7, Metastatic breast cancer (MBC): Metastatic breast cancer, also known as advanced , secondary or stage 4 breast cancer. This type of breast cancer has spread to more distant parts of the body such as the bones, liver, lungs or brain . 

30. . SUB-TYPES OF BREAST CANCER 30

31. Sub-types of Breast Cancer The subtypes of breast cancer are based on the genes, a cancer expresses. Hormone receptor positive breast cancer: About two-thirds of breast cancers are hormone receptor positive, which means that they need female hormones estrogen and/or progesterone to grow and reproduce. Estrogen receptor (ER) positive: The cells of this type of breast cancer have receptors that allow them to use the hormone estrogen to grow. Treatment with anti-estrogen hormone (endocrine) therapy can block the growth of these cancer cells. (Cont.) 31

32. Progesterone receptor (PR) positive: This type of breast cancer is sensitive to progesterone , and the cells have receptors that allow them to use this hormone to grow. Treatment with endocrine therapy blocks the growth of the cancer cells. Most people with hormone positive breast cancer will be recommended  hormone blocking therapy such as Tamoxifen, Anastrozole or Letrozole. Hormone receptor (HR) negative: This type of cancer doesn't have hormone receptors, so it won't be affected by endocrine treatments aimed at blocking hormones in the body. (Cont.) 32

33. HER2 positive breast cancer: HER2 positive breast cancer cells have too much of the protein called human epidermal growth factor receptor-2 on the surface of the cancer cells. These excess HER2 receptors promote the growth of the cancer cells. HER2 positive breast cancer may be either hormone receptor positive or negative and treated with the drug  Herceptin (Trastuzumab), which specifically targets HER2 positive breast cancer and has been proven to be a very effective. If the breast cancer is also hormone receptor positive, hormone blocking therapy may be recommended. (Cont.) 33

34. Triple negative breast cancer (TNBC): Triple negative breast cancer does not have any of the three receptors ER, PR, HER2 commonly found on breast cancer cells (lack estrogen, progesterone and HER2 receptors) . Around 15% of diagnosed breast cancers are triple negative type breast cancer. Mainly it affects the younger people with a BRCA1 gene mutation. Chemotherapy is generally recommended, as TNBC responds better than other types of breast cancer. TNBC can be more aggressive & difficult to treat as it likely to spread and/or recur. 34

35. 35 BREAST CANCER TYPES SUB TYPES Non-invasive B C Invasive B C Lobular Carcinoma In Situ (LCIS) Ductal Carcinoma In Situ (DCIS) Invasive Ductal Carcinoma (IDC) Invasive Lobular Carcinoma (ILC) Paget’s Disease (PD) Inflammatory B C (IBC) Phyllodes Tumour (PT) Locally Advanced B C (LABC) Metastatic B C (MBC) Hormone Receptor Positive B C HER 2 Positive B C Triple Negative B C Estrogen Receptor Positive Progesterone Receptor Positive Hormone Receptor Negative

36. . REFERENCES 36

37. References World Health Organization, International Agency for Research on Cancer, 2020. American Cancer Society: Breast cancer overview. 2020. Pradhan, Tripathi, Pradhan, Nature an Immunobooster for Breast Cancer, Book. Partridge India Publication, 2015. www.nationalbreastcancer.org/about-breast-cancer/ www.cancer.net/cancer-types/breast-cancer/introduction. www.cancercenter.com/types/ www.ncbi.nlm.nih.gov/pmc/ www.oncologygypro.esmo.org. www.bcpp.org/resource/breast-cancer-subtype/ 37

38. . Thank You 38