CA BREAST D r S ana - PowerPoint Presentation

1. CA BREAST Dr Sana ishtiaq FCPS R3 general surgery unit one UKSO prof tariq ghaffor sb

2. ObjectivesSurgical AnatomyInvestigationsDiagnosisTypes of CA breastTreatmentTake away message

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4. COMPARATIVE AND SURGICAL ANATOMY overlies the pectoral region.from the second rib above to the sixth rib or inframammary crease below. Medially it extends to the lateral border of the sternum and laterally it reaches the anterior axillary line or the mid-axillary line. males the breast tissue is rudimentary and about 2 cm in diameter; it lies deep to the areola and extends up to the areolar edge.

5. ANATOMYparenchyma consists of ductolobular and supportive tissue. terminal ductule together with the lobule, constitute the terminal ductal lobular unit, TDLU. The TDLU responds to a number of hormones: namely, estrogen, progesterone, prolactin and growth hormone. five to nine major lactiferous (milk) ducts carrying milk from the lobes. Approximately 10–100 lobules empty via ductules into a lactiferous duct.

6. INVETIGATION:

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8. Mammography Mammography in two planes and ultrasonographyDiagnostic mammogramScreening mammogramOther tests may include a breast MRI or ultrasound.

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11. Magnetic resonance imaging MRI of the breast ● Women with dense breasts or discordant or equivocal fndings on mammogram/ultrasonography; ● to distinguish scar from recurrence in women who have had previous breast conservation therapy for cancer; to assess multifocality and multicentricity and, in lobular cancer, high-grade ductal carcinoma in situ (DCIS); ● women with breast cancer (BRCA) gene or other genetic mutations or a strong family history; ● women with breast implants. Mri-guided biopsy may be performed for lesions not visible on ultrasonography or mammogram.

12. BIOPSYThe primary or main tumor is biopsied first. Types of possible biopsies include Fine-needle aspiration (FNA) or core biopsy (CB) uses needles of different sizes to remove a sample of tissue or fluid. vacuum-assisted core biopsy (VACB), Incisional biopsy removes a small amount of tissue through a cut in the skin or body.Excisional biopsy removes the entire abnormal area. .

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15. Hormone receptor statusWhen hormones attach to receptors inside breast cancer cells, they can cause cancer to grow. If found, these receptors may be targeted using endocrine therapy. There are 2 types of hormone receptors:Estrogen – plays a role in breast developmentProgesterone – plays a role in menstrual cycle and pregnancy

16. ImmunohistochemistryIHC can find estrogen and progesterone receptors in breast cancer cells. A pathologist will measure how many cells have estrogen and/or progesterone receptors and the number of receptors inside each cell.

17. Hormone receptor-positive Most breast cancers are HR+.There are 2 types of HR+ cells: Estrogen receptor-positive (ER+) cancer cells may need estrogen to grow. These cells may stop growing or die with treatment to block estrogen production or estrogen receptor signaling. Progesterone receptor-positive (PR+) cancer cells need progesterone to grow. It is thought that PR expression also suggests the tumor is estrogen dependent.HR+ breast cancer is treated with endocrine therapy, which blocks estrogen receptor signaling

18. Hormone receptor-negative Hormone receptor-negative (HR-) breast cells do not have either estrogen or progesterone hormone receptors. These cancers are sometimes simply called hormone negative. HR- cancers often grow faster than HR+ cancers. Both the estrogen and progesterone receptors need to be negative for breast cancer to be considered HR-

19. HER2 STATUS Human epidermal growth factor receptor 2 (HER2) is a protein involved in normal cell growth. It is found on the surface of all cells. When amounts are high, it causes cells to grow and divide. Too many HER2s is called HER2-positive (HER2+). You might hear it called HER2 overexpression or amplification.

20. TEST FOR HER2Immunohistochemistry (IHC) measures receptors. If the ihc score is 3+, the cancer is her2+. If the score is 0 or 1, it is considered her2-. If the score is 2+, further testing is needed

21. Biomarker testing specific DNA (deoxyribonucleic acid) mutations/alterations, protein levels, or other molecular features. choose the best treatment for you.Proteins are written like this: BRCA. Genes are written with italics like this: BRCA. HER2 and hormone receptor status are part of biomarker testing

22. Genetic Risk TestingAbout 1 out of 10 breast cancers are hereditary. Depending on your family history or other features of your cancerTests results may be used to guide treatment planning. Genetic testing is done using blood or saliva (spitting into a cup or a cheek swab). The goal is to look for gene mutations inherited from your biological parents called germline mutations. Some mutations can put you at risk for more than one type of cancer. You can pass these genes on to your children

23. BREAST CANCERThe most common types are either ductal or lobular.Ductal carcinoma starts in the cells that line the milk ducts. Milk ducts are thin tubes that carry milk from the lobules of the breast to the nipple. It is the most common type of breast cancer. Lobular carcinoma starts in the lobules (milk glands) of the breast. It is the second most common type of breast cancer.

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26. Pathology of breast cancer Milk ducts in 90% (ductal carcinoma) or from the lobule in 10% (lobular carcinoma) of patients. In situ disease. ‘Invasive or infltrative’ ductal or lobular carcinoma. The modified Bloom–Richardson scoring system for tumor grade includes the sum of individual scores for three variables (percentage of tumor cells with tubule formation, nuclear pleomorphic and the size and number of mitoses/HPF), each of which is assigned from 1 to 3 points according to the degree of deviation from normal breast epithelium. A total score of 3–5 defines grade I; 6 or 7 grade II; and 8 or 9 grade III.

27. Invasive carcinoma is usually of no special type (NST), which represents the most common variety of breast cancer. The tumor cells may overexpress estrogen receptors (ER positive), progesterone receptors (PR positive), human epidermal growth factor receptor 2/neu (HER2/neu positive) and androgen receptors (AR positive). The degree of mitosis can be detected by the Ki-67 mitotic index.

28. Gene array analysis five major subtypes: luminal A, luminal B, basal, HER2/neu receptor enriched and a normal-like group

29. Spread of cancer (desmoplastic reaction). (shortened single Cooper’s ligament), puckering or tethering (many Cooper’s ligaments shrunken) or nipple retraction.Lymph node spreadHematogenous spread

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31. Clinical presentation A discrete lump in the breast is the most common presentation, The most common tumour site is the upper outer quadrant of the breast (50% of tdlus lie there). Other symptoms include nipple retraction, nipple discharge (blood or serous), skin changes such as ulceration, peau d’orange , satellite nodules or dimpling/tethering.

32. Cancer staging Is used to reflect prognosis and to guide treatment decisions. It describes the size and location of the tumor and if cancer has spread to lymph nodes, organs, or other parts of the body. It also takes into account hormone receptor and her2 status. Staging includes: Anatomic – based on extent of cancer as defined by tumor size (t), lymph node status (n), and distant metastasis (m).Prognostic – includes anatomic tnm plus tumor grade and the status of the biomarkers such as human epidermal growth factor receptor 2 (her2), estrogen receptor (er), and progesterone receptor

33. Prognostic stages are divided into clinical and pathologic. Pathologic stage applies to those who have undergone surgery as the initial treatment for breast cancer. Clinical stage (c) is the rating given before any treatment. It is based on a physical exam, biopsy, and imaging tests. An example might look like cn2 or cm1.Pathologic stage (p) or surgical stage is determined by examining tissue removed during surgery. An example might be pn2. If you are given drug therapy before surgery, then the stage might look like ypt3

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36. Numbered stagesNumbered stages are based on TNM scores and receptor (hormone and HER2) status.stage 0, stage I, stage II, stage III, and stage IV. Stage 0 is Noninvasive breast cancer is rated stage 0. Ductal carcinoma in situ (DCIS) is found only in the ducts (Tis). It has not spread to the surrounding breast tissue, lymph nodes (N0), or distant sites (M0). Stages 1, 2, and 3 are invasive breast cancer. It has grown outside the ducts, lobules, or breast skin. Cancer might be in the axillary lymph nodes. Stage 4 is metastatic. In stage 4 breast cancer, cancer has spread to distant sites. It can develop from earlier stages. Sometimes, the first diagnosis is stage 4 metastatic breast cancer (called de novo)

37. prognostic and predictive biomarkers The steroid hormone receptor pathway; Human epidermal growth factor receptor 2 (HER2)/ neu,(egfr), transforming growth factor, platelet-derived growth factor, and the insulinlike growth factor family; Proliferating cell nuclear antigen (PCNA) and ki-67; (VEGF) and the angiogenesis index; the mammalian target of rapamycin (mtor) signaling pathway; Tumor-suppressor genes such as p53;The cell cycle, cyclins, and cyclin-dependent kinases;

38. Steroid Hormone Receptor Pathway Breast cancer risk is related to estrogen exposure over time. In postmenopausal women, hormone replacement therapy consisting of estrogen plus progesterone increases the risk of breast cancer by 26% Patients with HR +ve tumors survive two to three times longer after a diagnosis of metastatic disease than do patients with HR –ve tumors.

39. Tumor positive for estrogen or progesterone receptors have a higher response rate to endocrine therapy than tumors that do not express estrogen or progesterone receptors. Testing for estrogen and progesterone receptors should be performed on all primary invasive breast cancer specimens.

40. HER2/ neu is both an important prognostic factor and a predictive factor in breast cancer. When overexpressed in breast cancer, her2/neu promotes enhanced growth and proliferation, and increases invasive and metastatic capabilities. Her2/neu–overexpressing breast cancer have poorly differentiated tumors with high proliferation rates, positive lymph nodes, decreased hormone receptor expression, and an increased risk of recurrence and death due to breast cancer.

41. Tumors show HER2 amplification or HER2/neu protein overexpression are candidates for anti-her2/neu therapy. Trastuzumab (herceptin) is a recombinant humanized monoclonal antibody directed against her2.Single-agent trastuzumab therapy is well tolerated and active in the treatment of women with her2/neu–overexpressing metastatic breast cancer.

42. TreatmentThe treatment of breast cancer is multimodal (includes surgery, systemic treatment [chemotherapy, targeted therapy, hormonal therapy] and radiotherapy].

43. Neoadjuvant systemic therapy (NAST) :Downsize the disease and enable clinicians to know the in vivo response of the tumour to therapy. Indications for : 1) locally advanced breast cancer t3, t4/n2, n3 disease: to downsize the tumour. 2) select cases of early breast cancer: A; to downsize the tumour to facilitate breast conservation surgery (BCS); b HER2/neu-positive tumours; C; triple-negative breast cancer (TNBC); D; premenopausal women (age <50 yrs), patient with axillary metstasis.

44. Neoadjuvant targeted therapy (trastuzumab, pertuzumab) is administered for HER2/neu-positive tumours >5 mm in diameter. Neoadjuvant hormonal therapy is ofered to elderly or frail women (with er and/or -, pr-positive advanced tumours) who are deemed unfit to receive systemic chemotherapy. Neoadjuvant hormonal treatment takes longer (around 3–6 months) for the response to become clinically evident.

45. Response assessment and timing of surgery: the patient is examined 3 weeks after administration of the second cycle of NACT.Response evaluation criteria in solid tumours (RECIST) are used for reporting the response to NAST.

46. RECIST The four categories are: complete response (CR) (lesion not detectable on clinical palpation and imaging); partial response (PR) (≥30% reduction in the maximal diameter); stable disease (SD) (< 30% reduction in the maximal diameter)progressive disease (PD) (≥20% increase in the maximal diameter).

47. For patients with CR and PR, the entire chemotherapy regimen may be delivered prior to surgery.

48. Surgical management The aim of surgery is to remove all disease in the breast and axilla with negative margins. .

49. Early breast cancer (stages 0, I ,II) The surgical options for the primary tumour include mastectomy or BCS. Mastectomy is indicated for large tumours (in relation to the size of the breast), multicentric disease, diffuse microcalcifcation on a mammogram indicative of DCIS, BRCA-positive cancers, local recurrence following BCS or the patient’s preference.

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52. Mastectomy by surgical unit

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54. Skin- and nipple-sparing mastectomy In DCIS and early breast cancers where a mastectomy is indicated and the tumour is >1  cm away from the skin and >2  cm away from the nipple. (Bcs) is aimed at removing the tumour along with a 1-cm margin of normal breast tissue. Surgical specimen with sutures: long lateral (‘l’ for ‘lateral’) and short superior (‘s’ for ‘superior’). All patients with BCS receive radiotherapy. Bcs together with radiotherapy is called breast conservation therapy (BCT): BCS + RT = BCT. ).

55. Wide local excision (WLE) of up to 20% of the breast volume can be achieved by excision of the tumour with adequate margins and closure of the defect by approximation of the breast tissue with absorbable sutures. . Oncoplasty is defned as tumour excision with wide margins followed by repair of the defect by local rearrangement/ replacement of the breast tissue and the nipple–areola complex to maintain shape and symmetry.

56. Surgery for the axilla The role of axillary surgery is to stage the patient (sentinel lymph node biopsy [SLNB]) and to treat disease by axillary lymph node dissection (ALND) for patients with positive axillary nodes.

57. Axillary lymph node dissection

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59. Surgical options for locally advanced breast cancers (stages IIIA, IIIB) Following NACT patients should be ofered the option of mastectomy or BCS, if suitable Patients with initial skin or chest wall involvement and those with infammatory carcinoma should undergo MRM

60. Adjuvant treatment Radiotherapy. The indications include the following: ● patients with locally advanced breast cancers T3, T4, N1, N2, N3 disease; ● following BCS; ● after mastectomy if: tumour size ≥5  cm; skin or chest wall involvement; lymphovascular invasion (LVI), grade 3; axillary lymph node positive for metastasis

61. In pathologically lymph node-negative tumours, radiotherapy after BCS is given to the breast only as a dose of 45–50.4 Gy (with or without a boost) delivered in 25 fractions or of 40–42.5 Gy delivered in 15 or 16 fractions (hypofractionation). In patients after mastectomy (T3N0M0), chest wall radiotherapy is given if the sentinel lymph nodes are negative. In patients with lymph node-positive disease locoregional radiotherapy is given covering the chest wall, supraclavicular region, internal mammary nodes and the axilla. The axilla should not be irradiated after axillary node dissection as this increases the risk of lymphoedema.axillary lymph node positive for metastasis.

62. Adjuvant systemic therapy The purpose of adjuvant systemic therapy is to control putative micrometastases, delay relapse and prolong survival.

63. Chemotherapy. This is the most common systemic treatment for breast cancer. Adjuvant chemotherapy is indicated for all invasive carcinomas >1  cm in diameter, tumours >0.5  cm with prognostic factors (presence of LVI, high grade, HER2/neu positive, TNBC) and node-positive tumours.

64. Targeted therapy The monoclonal antibody trastuzumab (Herceptin®) is efective against the HER2/neu receptor. It is used along with pertuzumab to treat HER2/neu-positive tumours along with chemotherapy.

65. Hormone therapy.The selective oestrogen receptor modulatorAromatase inhibitors are used in postmenopausal women; . Bisphosphonates with vitamin D and calcium are used to restore bone loss and may also reduce the risk of recurrence.

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67. Follow-up of operable breast cancer Follow-up after initial therapy routinely includes clinical examination every 3 months for 2 years, followed by every 6 months for the next 3 years. Thereafter the follow-up is scheduled yearly. A mammogramPatients presenting with metastatic disease and those with a local/systemic recurrence are seen more frequently depending on the clinical condition

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