BREAST

1. BREAST

2. INCIDENCE • Second most common type of cancer after lung cancer (10.4% of all cancer incidence, both sexes counted) • Fifth most common cause of cancer death • Hundred times more common in female • Lower in less-developed countries and greatest in the more-developed countries

3. CLASSIFICATION • Pathology • Tumor Grade • well-differentiated (low grade) • moderately differentiated (intermediate grade) • poorly differentiated (high grade) • Protein and Gene expression • Tumor Stage

4. CLINICAL FEATURES • Lump breast • Palpable L nodes (axilla,supraclavicular) • skin dimpling • nipple inversion • spontaneous single-nipple discharge • Pain (unreliable) • Inflammatory Breast Ca (pain, swelling, warmth and redness, Peau d orange)

5. Paget’s disease of breast (tingling, itching, increased sensitivity, burning, nipple disch, pain) • Metastasis (bone, liver, lung and brain) • Unexplained weight loss • fevers or chills • Bone or joint pains • jaundice or neurological symptoms

6. EPIDEMIOLOGY/ETIOLOGY • Genetic mutations • Abnormal growth factors • Failure of immune surveillance • Inhertited defects in DNA repair genes (BRCA1, BRCA2, p53)

7. RISK FACTORS • Sex • Age • Childbearing • Hormones • high-fat diet • alcohol intake, tobacco use • Obesity • radiation

8. Hereditary syndromes (5%) • carriers of the breast cancer susceptibility genes, BRCA1 and BRCA2, are at a 30-40% increased risk for breast and ovarian cancer

9. PREVENTION • Lower age of first childbirth (less than 24 years maternal age) • having more children (about 7% lowered risk per child) • breastfeeding (4% per breastfeeding year, with an average relative risk around 0.7)

10. Phytoestrogens (soy) • Folate • Oophorectomy / (mastectomy) • Hormonal therapy • SERM’s (Tamoxifen, Raloxifene)

11. SCREENING • self and clinical breast exams • x-ray mammography • breast MRI • Genetic testing (BRCA mutations)

12. DIAGNOSIS • TRIPPLE ASSESMENT • Clinical Assesment • Radiology (Mammography, USS) • Tissue Dx (FNAC, Trucut)

13. STAGING • TX: Primary tumor cannot be assessed. T0: No evidence of tumor. Tis: Carcinoma in situ, no invasion T1: Tumor is 2 cm or less T2: Tumor is more than 2 cm but not more than 5 cm T3: Tumor is more than 5 cm T4: Tumor of any size growing into the chest wall or skin, or inflammatory breast cancer

14. NX: Nearby lymph nodes cannot be assessed N0: Cancer has not spread to regional lymph nodes. N1: Cancer has spread to 1 to 3 axillary or one internal mammary lymph node N2: Cancer has spread to 4 to 9 axillary lymph nodes or multiple internal mammary lymph nodes N3: Cancer has spread to 10 or more axillary lymph nodes, ,OR supra/subclavicular nodes or axillary lymph nodes and has enlarged the internal mammary lymph nodes, or Cancer involves 4 or more axillary lymph nodes

15. MX: Presence of distant spread (metastasis) cannot be assessed. M0: No distant spread. M1: Spread to distant organs, not including the supraclavicular lymph node, has occurred

16. TUMOR MARKERS • Ca 15.3 (carbohydrate antigen 15.3, epithelial mucin) is a tumor marker determined in blood which can be used to follow disease activity over time after definitive treatment

17. Mammogram(Breast Cancer)

18. STAGES • Stage 0 - Carcinoma in situ (DCIS) • Stage I - Tumor (T) does not involve axillary lymph nodes (N). • Stage IIA – T 2-5 cm, N negative, or T <2 cm and N positive. • Stage IIB – T > 5 cm, N negative, or T 2-5 cm and N positive (< 4 axillary nodes). • Stage IIIA – T > 5 cm, N positive, or T 2-5 cm with 4 or more axillary nodes • --------------------------------------------------------------------- • Stage IIIB – T has penetrated chest wall or skin, and may have spread to < 10 axillary N • Stage IIIC – T has > 10 axillary N, 1 or more supraclavicular or infraclavicular N, or internal mammary N. • Stage IV – Distant metastasis (M)

19. HORMONE RECEPTORS • Breast lesions are examined for certain markers, notably sex steroid hormone receptors. About two thirds of postmenopausal breast cancers are estrogen receptor positive (ER+) and progesterone receptor positive (PR+). Receptor status modifies the treatment as, for instance, only ER-positive tumors, not ER-negative tumors, are sensitive to hormonal therapy

20. HER 2 • The breast cancer is also usually tested for the presence of human epidermal growth factor receptor 2, a protein also known as HER2, neu or erbB2. • HER2 accelerates tumor formation. About 20-30% of breast cancers overexpress HER2. • Those patients may be candidates for the drug trastuzumab(Herceptin), both in the postsurgical setting (so-called "adjuvant" therapy), and in the metastatic setting

21. Surgery • D.C.I.S. • Operable breast cancer. • Locally advanced disease.

22. Non surgical treatment • Adjuvant chemotherapy. • Adjuvant hormone treatment. • Adjuvant Radiotherapy. • Neo-adjuvant Chemotherapy.

23. Surgery for early breast cancer • Non invasive breast cancer (DCIS): - No absolute consensus. - Lesions < 4cm: WLE with 1cm safety margin. No axillary surgery. - Lesions > 4cm or multifocal consider mastectomy. - Axillary node sampling if extensive multifocality (1-5% lymph node involvement) ( Dixon 1998) - DXT: beneficial - Hormonal treatment: less certain ( Lancet IBIS trial 2003). • Lobular carcinoma in situ (LCIS): a marker lesion for increased risk of invasive cancer/close surveillance.

24. WLE

25. WLE+ Augmentation Mammoplasty

26. Invasive Breast Cancer (Early) • Breast Conservative Tumour (BCT): solitary <3cm, or selected cases with > 3cm in large breast (MDM). • Contraindications: - multifocal, - recurrent disease after BCT, - patient choice, - tumour > 3cm, - centrally placed tumors, or - if DXT is contraindicated, - pregnancy, - age< 35 years( MDM).

27. Breast Conservative Surgery (BCS) • A cylinder of breast tissue from skin to deep fascia is removed. • No skin is removed unless superficial tumor. • Macroscopic radial margins should be at least 10-20mm and microscopic margins at least 5mm. • Radiopaque clips: 1( anterior surface),2(medial surface), 3(inferior surface). • Silk suture on tissues closest to nipple.

28. Breast conservative surgery

29. What’s next • Specimen x ray for all cases with a detectable mammographic abnormality. • If close margin: immediate re-excision at same operation. • 4 axillary node sampling if axillary clearance is not indicated. • ER and PR status in all patients. • Mark the cavity with 4 clips on the pectoral fascia for DXT( superior, inferior, medial and lateral).

30. Treatment of axilla • Incidence: 1%(DCIS),5%-28%(T1), 48%(T2), 68%(T3), 88%(T4). • Axillary sampling (4 node): - if clinically N0 • Axillary clearance: if N1 or +FNAC and if mastectomy is indicated for recurrent disease. • Not indicated if previously treated with radiotherapy.

31. Locally advanced Breast Cancer • large cancer(T3-4), skin or muscle or chest wall infiltration, matted L.N. • Full screen for metastasis( bone scan, liver US, possible CT chest). • MDM: select cases for adjuvant chemotherapy and hormonal ttt (Cancer;98:1150-60, 2003).

32. Locally advanced Breast Cancer • Hormonal: slowly growing, ER PR+, unfit patients for chemotherapy. • Chemotherapy: inflammatory carcinoma, ER, PR –ve, young patient <35. • Value: down staging, • Definitive surgery will entirely depend on the tumor response.

33. Chemotherapy • Adjuvant( in addition)/Neo-adjuvant (in advance/instead) of surgery. • Details pathology: tumour size, grade, nodal, receptor status, margins of excision and the presence or absence of vascular or lymph-vascular invasion. • Indications (risk factors): +ve nodes, grade 2-3, size>2cm,vascular invasion and receptor –ve tumors. • Anthracycline based e.g. 6 cycles of Epirubicin,5FU, Cyclophosphamide. Other combinations Epirubicin, Cyclophosphamide and Taxane.

34. Chemotherapy continued • HER2 receptor status is becoming increasingly important particularly in relapse patients who are candidates for Trastuzumab (Herceptin). • The benefits of chemotherapy in postmenopausal patients is increasingly appreciated making the traditional classification of patients into pre and post menopausal less crucial. • Chemotherapy is not routinely offered to patients>65years.

35. Hormonal therapy • All patients with estrogen/ progesterone receptors positive. • Tamoxifen 20mg/day for 5 years. • Exceptions: previous tamoxifen therapy or history of thrombo-embolism. • Should not simultaneously prescribed with DXT for fear of increased risk of pulmonary fibrosis. (Radiother Oncol 2002,Br J Cancer 2004). • Should not simultaneously prescribed with chemotherapy as it reduce its effect and significantly increase the incidence of thromboembolism. • ATTOM trial 5 more years of tamoxifen after finishing a 5 year treatment. Provided that the patients are disease free and had a complete resection of tumors.

36. Arimidex (Anastrozole) • A non steroidal aromatase inhibitor. • ATTAC trial suggests: it is stronger with better prognosis and lesser side effects than tamoxifen. • Nevertheless more arthralgia and fractures complication (Lancet 2005). • Receptor +ve postmenopausal.

37. Adjuvant Radiotherapy • Post BCS: DXT is given to the breast and the lower axilla in the tangential glancing fields. • DXT should be considered for all patients with completely excised DCIS who had undergone BCS. • Only those with lesions <10mm should be discussed at the MDM. • 4500-5000 cGY in 20-25 fractions daily. Options to give boost in younger patients. • DXT to supraclav. L.N: Should be considered with 4 or more pathologically involved axillary L.Ns, apical nodes involvement and with extra nodal spread of tumor.

38. Post-mastectomy Radiotherapy • Chest wall: - 4 or more pathologically involved axillary nodes, - primary tumor >5cm(large breast) - and tumor 3-5cm( small breast), - narrow deep margin <0.5cm, - evidence of lymph vascular invasion. • Irradiation to the axilla is only for those who have not had axillary clearance.

39. Follow up • Access to breast care nurse/unscheduled outpatient review and for post 5 years follow ups. • Patients are seen for 5years in the breasts cancer follow up clinic starting from 2 weeks postoperative where the results are conducted. • Alternating appointment every 3months between the oncologist and the surgeon for 2 years, then very 6 months for 3years. • Clinical examination to the breast and the lymph nodes.

40. Follow UP • Mammography is requested annually for 5 years. • After 5 years if < 50years, arrange biennial mammography until 50years. • if>50years then discharge to NHSBSP for 3yearly screening. • IF>70years self referral for 3yearly screening. • All patients diagnosed with distant metastasis should stop mammography surveillance. • Other investigations are only requested if symptoms develop e.g. back pain, lump, rash etc

41. Breast reconstruction • Patients should be aware prior to surgery for the possibility of breast reconstruction. • Primary? Delayed? • All patients should be offered the opportunity to meet another patient who underwent BR.

42. Breast Reconstruction

43. Breast reconstruction

44. Outcome of breast cancer • 60% of patients will develop some form of recurrence, 2/3(40%) will develop within 5 years. • 50% will eventually present with distant metastasis and die from the disease. • Nottingham prognostic index (NPI): Grade(1-3)+ N Stage (N 0-2)(1-3)+ (0.2xsize of tumor in cm)

45. Outcome of breast cancer • No (negative axilla), N1 (low axilla}, N2 (high axilla). • Good (score<3.4)(80% 10 year survival ),moderate (score 3.4-5.4)(40% 10 year survival) , poor (score >5.4) (15%10 year survival). • Example: 2cm,G2,N1= 0.4+2+2= 4.4 =moderate

46. PROGNOSIS • Stage • Grade • Age (younger women worse prognosis) • ER, PR • HER2

47. Breast Pain (cyclical or not) • No mass, mild pain: - <35 years: reassure and discharge. - > 35 years: mammography • No mass, moderate to severe pain: - < 35: ultrasound - > 35: mammography • Good support bra night and day, reduce caffeine intake, discontinue smoking, low fat diet, change the type of contraceptive pills and • Evening primrose capsules: - Gamolenic acid 240-300mg - 3-4 months at least - Danazol 100mg daily, assess after one month and continue for 6 months if response.

48. Cystic disease ( fibrocystic or not) • Palpable cysts, 7% of western women. • U/S, Mammography according to the age group. • Aspirate (free hand or ultrasound): - No blood, no residual lump, not re-accumulating: discharge - Rapidly recurrent, or blood: re-image, FNAC ?excision? • Multidisciplinary meeting (MDM).

49. Diagnosis • Breast lump, asymmetric thickening, nodularity, nipple discharge. • Triple assessment: clinical examination, radiological (ultrasound, mammography), Biopsy( wide bore needle, FNAC). • P value, U value, R value: 1-5(normal, benign, uncertain, suspicious, malignant). • Any P3,U3, R3 should be biopsied. • One stop clinic: patient will be given another appointment for the results if P3,U3,R3. • FNAC is only used with too small or inaccessible lesions and with nipple discharge. • All discordant results should be discussed in the MDM.

50. Ultrasound/Mammography • Ultrasound: breast abnormalities in ages <35 years, however, • It should not used in pain, and not as screening tool. • Mammography: - Breast abnormalities in ages >35 years. - National screening programme >50 years. - Early Screening (age < 50years,+family). - Nipple discharge. - Follow up in diagnosed breast cancer.