Pathology and management of carcinoma breast

All about carcinoma breast

1. CARCINOMA BREAST PROF . DR. S.P. GAYATHRE M.S., D.G.O., PROFESSOR AND HEAD OF DEPARMENT DEPARTMENT OF GENERAL SURGERY GOVT STANLEY MEDICAL COLLEGE AND HOSPITAL

2. CLASSIFICATION OF BREAST CANCER Primary breast cancer Non Invasive epithelial cancer Invasive epithelial cancer Mixed connective and epithelial tumors

3. NON INVASIVE EPITHELIAL CANCER Carcinoma in situ – Not breaching basement membrane Does not metastasize.

4. DUCTAL CARCINOMA IN SITU DCIS - clonal proliferation - limited - basement membrane Myoepithelial cells - preserved D etected - mammography-calcifications due to secretory material necrosis periductal fibrosis

5. Morphology Comedo DCIS Cribriform DCIS Micropapillary DCIS Papillary DCIS

6. Comedo DCIS C lustered/Linear/Branching calcification Tumor cells - pleomorphic,high -grade Nuclei C entral necrosis

7. Cribriform DCIS Rounded (cookie cutter–like) spaces

8. Micropapillary DCIS Complex bulbous protrusions without fibrovascular cores

9. Papillary DCIS True papillae with fibrovascular cores that lack a myoepithelial cell layer

10. Paget’s disease of nipple Malignant condition M/C Post menopausal women Gradual destruction - Nipple & Areolar complex Eczema of Nipple - Bilateral , P aget’s - Unilateral ER-negative, overexpress HER2 .

11. CLINICAL FEATURES Underlying Lump is usually present Edges - Distinct Itching Absent Vesicles Absent DIAGNOSIS Nipple Biopsy Cytological Preparation Of Ex u dates

12. INVASIVE CARCINOMA Invasive ductal carcinoma Invasive lobular carcinoma

13. INVASIVE DUCTAL CARCINOMA Adenocarcinoma with No special type ( 50 -70%) SPECIAL TYPES Tubular carcinoma (2-3) Cribriform carcinoma (1-3%) Mucinous or colloid carcinoma (2-3%) Papillary carcinoma(1-2%) Adenoid cystic carcinoma (1%) Metaplastic carcinoma (1%)

14. Special types of invasive ductal carcinoma Tubular carcinoma : W ell formed tubules

15. Mucinous or colloid carcinoma ; Tumor cells - arranged in clusters S mall island of cells within - lake of mucin

16. Medullary carcinoma solid sheets of large cells pleomorphic nuclei prominent nucleoli, Frequent mitotic figures,

17. Metaplastic carcinoma includes spindle cell carcinomas and matrix-producing carcinomas .

18. Papillary carcinoma True papillae - fronds of fibrovascular tissue

19. Invasive lobular carcinoma L oss of CDH1 - E cadherin Lobular carcinomas are dyscohesive , D ifficult to palpate or image Indian file pattern

20. MIXED CONNECTIVE AND EPITHELIAL TUMORS Phyllodes tumor Its spectrum covers both benign and malignant course In malignant course , the features such as: 1 ) Cellular atypia 2 ) Mitotic figure 3 ) Stromal overgrowth

21. Angiosarcoma A rising - parenchyma or dermis of breast Types 1. primary 2.secondary Primary angiosarcoma Secondary angiosarcoma : after surgery or irradiation

22. MOLECULAR CLASSIFICATION OF BREAST CANCER Luminal a ER AND PR + HER2/ neu - Ki -67 low Luminal b ER AND PR + HER2/ neu - Ki-67 high HER2/ neu enriched ER- PR- HER2/ neu + Ki-67 high Triple negative ER- PR- HER2/ neu - Ki-67 high Claudin low ER- PR- HER2/ neu - Claudin low

23. RISK FACTORS FOR BREAST CANCER

24. Clinical Features PAINLESS LUMP M ay be associated with indrawing of nipple M/C upper outer quadrant(60%) Short History & Fast Growth Uneven Shape & Surface Margin – Well Defined & irregular

25. NIPPLE DISCHARGE is the second common presentation DISCHARGE Single Duct Serous Ductectasia Multiple Duct Blood Stained Carcinoma From Surface Yellow / Bloody Paget’s Disease

26. PEAU D'ORANGE : Dermal lymphatic obstruction

27. SKIN CHANGES DIMPLING OF SKIN: DUE TO INFILTRATION OF SINGLE LIGAMENT OF COOPER PUCKERING/ TETHERING SKIN : DUE TO MULTIPLE LIGAMENT OF COOPER INVOLVEMENT

28. RETRACTION OF NIPPLE: • INFILTRATION & FIBROSIS OF LACTIFEROUS DUCT • RECENT HISTORY OF RETRACTION - SEEN CARCINOMA CANCER-EN-CUIRASSE: ARMOUR COAT

29. SKIN ULCERATION & FUNGATION : RED WEEPING ULCER –PAGET’S DISEASE FUNGATION - LATE FEATURE -ADVANCED CA BREAST LYMPHNODE ENLARGEMENT COMMONLY INVOLVED : AXILLARY & SUPRACLAVICULAR

30. INVESTIGATIONS AND STAGING OF BREAST CANCER

31. IMAGING 32 Mammography Ultrasonography Magnetic Resonance Imaging Positron emission tomography

32. MAMMOGRAPHY 33 Screening/ diagnostic Used - >40 years of age.

33. MAMMOGRAPHY 34 X- ray of the breast. P lacing the breast - direct contact with ultrasensitive film - exposing - low voltage, high current x- rays. Dose of radiation per film : 1mGy

34. MAMMOGRAPHY – VIEWS 35 2 Types of views – Craniocaudal view Mediolateral oblique view MEDIOLATERAL OBLIQUE VIEW Breast compressed diagonally. Provides side view of breast. More breast tissue is visualised and axilla is appreciated. CRANIOCAUDAL VIEW Breast compressed horizontally. Provides top- view of the breast. Deep medial breast tissue can be visualized, provides maximum compression.

35. BIRADS SCORE Reference – Bailey & Love’s Short practice of surgery Developed by the American College of Radiology, it is a standardized way of reporting any imaging study of the breast.

36. ULTRASONOGRAPHY Imaging modality of choice: To differentiate between solid and cystic mass. A pregnant lady with a lump. Young female dense breast. USG shows a solid, irregular-shaped mass, taller than wider, with angular irregular margins. (BI-RADS) score 5

37. MAGNETIC RESONANCE IMAGING BRCA Positive Inconclusive USG. M ultifocal and multi-centric lesions. Imaging investigation of choice to identify local/scar recurrence after surgery. Breast implants .

38. Metastatic work-up 20XX Pitch Deck 39 Done for patients with locally advanced breast disease. Contrast Enhanced CT of chest Ultrasound of abdomen Isotope bone scan

39. HISTOPATHOLOGY Fine Needle Aspiration Cytology (23 – 30G) thin needle used. Cells should be taken from representative area. Indications of FNAC in breast lesions : • C ystic breast lesion. • Axillary lymph node cytology. CNB > FNAC because •Tissue is obtained. •Can differentiate between in-situ and invasive cancer. •ER, PR, HER 2 neu status •Less false negative rate.

40. CORE NEEDLE BIOPSY Also known as Tru–cut biopsy 14-18 G needle used Can be taken under image guidance. Should be taken from solid part of the lesion.

41. 42 T STAGE Tx Cannot be assessed T0 No evidence of tumor Tis (in situ) DCIS Paget’s T1 mi </=1mm (microscopic) a 1mm – 5mm b 5mm – 10mm c 1cm - 2cm T2 >2cm, </= 5cm T3 >5cm T4 a Chest wall involvement b Skin involvement c a + b d Inflammatory ca breast, worst prognosis. N STAGE Nx Cannot be assessed N0 No lymph nodes N1 Mobile axillary lymph node N2 a Fixed axillary lymph node b Internal mammary node + Axillary lymph node - N3 a Infraclavicular lymph node b Internal mammary node+ axillary lymph node + c Supraclavicular lymph node M STAGE M0 No distant metastasis M1 Distant metastasis present TNM STAGING

42. BREAST CONSERVATION THERAPY

43. CONTENTS Definition Advantages Indications Contraindications Procedure of BCS Radiotherapy Follow up Complications

44. BREAST CONSERVATION THERAPY : BCT involves wide local excision of the tumor [BCS] with axillary dissection with radiotherapy to the breast and chest wall BCT=BCS+RADIOTHERAPY

45. INDICATIONS Tumor s - excision with clear margins Small tumor to breast ratio

46. CONTRAINDICATIONS ABSOLUTE CONTRAINDICATIONS RELATIVE CONTRAINDICATIONS FIRST TRIMESTER PREGNANCY PRIOR RADIATION THERAPY TO CHEST WALL MULTICENTRIC TUMORS SCLERODERMA EXTENSIVE DUCTAL CARCINOMA IN SITU RHEUMATOID ARTHRITIS INFLAMMATORY BREAST CANCER LI-FRAUMENI SYNDROME LARGE TUMOR TO BREAST RATIO EXTENSIVE POSITIVE PATHOLOGICAL MARGINS

47. PROCEDURE OF BCS: CURVILINEAR SKIN INCISION/ RADIAL INCISION TUMOR IS REMOVED ALONG WITH AN ENVELOPE OF NORMAL APPEARING TISSUE ACHIEVE A CANCER FREE MARGIN MASS IS REMOVED SPECIMEN IS MARKED WITH SHORT SUPERIOR , LONG LATERAL SUTURES SPECIMEN MAMMOGRAM or FROZEN SECTION BIOPSY AXILLARY DISSECTION is done Cavity is labelled with clips –RADIOTHERAPY Sutures to close the cavity Post op scarring is minimal

48. RADIOTHERAPY Recurrence rates are too high - surgery alone P ost operative radiation - 45-50.4 Gy delivered in 25 fractions In patients with lymph node-positive disease locoregional radiotherapy is given covering chest wall,supraclavicular regions,internal mammary nodes and axilla

49. APBI-ACCELERATED PARTIAL BREAST IRRADIATION INDICATIONS : Women of 50 years or older with T 1 disease and negative resected margins with margin width of 2mm Invasive ductal carcinoma ER positive,BRCA negative and sentinel nodes negative

50. FOLLOW UP BILATERAL MAMMOGRAPHY After 6 To 12 Months Annual Screening Mammogram Biannual B reast Examination

51. COMPLICATIONS Hardness due to scar tissue Change in size and shape of breast Seroma Lymphedema if lymph nodes were involved Recurrence

52. MANAGEMENT OF EARLY BREAST CANCER

53. What is EARLY BREAST CANCER ? Breast cancer that has not spread beyond the breast or axillary lymph nodes. This includes  Insitu breast cancer - Stage 0  Stage I  Stage II A  T2 NI M0 of stage II B

54. AIMS OF TREATMENT  CURE  CONTROL of local disease  CONSERVATION of breast  Prevention of LOCAL RECURRENCE  Prevention of DISTANT METASTASIS

55. SURGERY PRIMARY TUMOR LYMPH NODE BREAST CONSERVATION SURGERY MASTECTOMY N0 STATUS LYMPH NODE INVOLED SENTINEL LYMPH NODE BIOPSY AXILLARY LN CLEARANCE

56. TYPES OF MASTECTOMY Modified radical mastectomy Simple mastectomy Skin sparing mastectomy Toilet mastectomy Extended radical mastectomies Halsted radical mastectomy

57. MODIFIED RADICAL MASTECTOMY  removal of breast + nipple areolar complex + pectoral fascia + level 1 , 2, 3 axillary lymph node s Patey’s operation - removed Scanlon operation - incised Auchincloss operation - retracted

58. Large tumours (size compared to the breast) Multicentric disease DCIS (diffuse microcalcification on a mammogram) BRCA positive tumours Local recurrence following BCS Patients preference INDICATIONS FOR MRM

59. PROCEDURE FOR MRM: POSITION :-  The Patient is placed in supine position  Ipsilateral arm extended and placed at 90° with a sandbag placed below the scapula. Under General Anesthesia INCISION :-  Stewart’s elliptical incision pointing towards the axilla  

60.   STEWART’S INCISION

61. Skin incision is made. Skin flaps are raised after providing traction using skin hooks with monopolar cautery. Extent of flaps: Laterally till the anterior border of latissimus dorsi Medially till the parasternal edge Superiorly ti ll inferior border of clavicle Inferiorly till the inframammary crease  PROCEDURE OF MRM

62. Skin flaps

63. 4. Inferior flap is more adherent and difficult to raise. 5.Skin flap should be of adequate thickness to prevent flap necrosis. 6.Breast tissue is removed along with pectoral fascia. 7.Axillary clearance is done.

64. AXILLARY CLEARANCE INDICATION  Early breast cancer  L ocally advanced breast cancer  C linical involvement of nodes  FNAC of lymph node or sentinel lymph node biopsy --proven malignancy LIMITS Superior  - Axillary Vein Inferior   - Angular Vein Lateral     - Thoracodorsal Pedicle Medial      - Halstead’s Ligament

66. Axillary lymph node dissection requires careful anatomical dissection to protect A xillary vein T horacodorsal vessels and nerves M edial and lateral pectoral nerves I ntercostobrachial nerves L ong thoracic nerve AXILLARY LYMPH NODE DISSECTION

67.   Seroma—50–70% Flap necrosis  Lymphedema (15%)  COMPLICATION OF MRM

68. Stewart Treves Syndrome

69. COMPLICATION OF MRM Bleeding Injury to nerve Intercostobrachial nerves--> altered sensation Long thoracic nerve --> Winging of scapula Thoracodorsal nerve Lateral and medial pectoral nerve Local recurrence --> MRI,Biopsy Cancer en cuirasse Phantom breast syndrome -->ICBN neuralgia

70. Winging of scapula Cancer en cuirasse

71. Skin sparing mastectomy Mastectomy + breast skin envelope is preserved and nipple–areola complex removed  Skin and Nipple sparing Mastectomy Mastectomy + breast skin envelope and nipple–areola complex are preserved. Simple or Total Mastectomy Only the Breast tissue along with the axillary tail is removed  OTHER PROCEDURE:

72. Simple mastectomy

73. Radical mastectomy Breast+nipple /areola complex+pectoralis fascia+pectoralis major+pectoralis minor+axillary lymph node level – 1,2,3 Extended radical mastectomy Radical mastectomy + internal mammary lymph node Toilet mastectomy In locally advanced cancer,tumor with breast tissue and whatever possible is removed to prevent further fungation . OTHER PROCEDURE

74. MANAGEMENT OF LOCALLY ADVANCED BREAST CANCER

75. CONTENTS DEFINITION TREATMENT OF LABC ꞏ Chemotherapy ꞏTargeted therapy ꞏNeoadjuvant chemotherapy ꞏTreatment for non-responders ꞏTreatment for responders Surgery Adjuvant chemotherapy Hormonal therapy

76. LOCALLY ADVANCED BREAST CANCER DEFINITION: Locally advanced breast cancer include large primary tumor (>5 cm), Tumors infiltrating the chest wall, Skin involvement, Inflammatory carcinoma, Bulky or fixed axillary node, and clinically apparent internal mammary or supraclavicular nodal involvement.

77. LOCALLY ADVANCED BREAST CANCER It includes stage IIB(T3 N0 M0) and stage III of TNM staging

78. TREATMENT: Neoadjuvant chemotherapy Responders Stable disease Surgery Chemotherapy Hormonal therapy Progressive disease

79. CHEMOTHERAPY INDICATIONS: 1. For all invasive carcinomas >1 cm in diameter 2. Tumors >0.5 cm with poor prognostic factors(HER-2 positive, TNBC) 3. In advanced carcinoma, Stage IV breast cancer as a palliative chemotherapy. 4. In inflammatory carcinoma of breast. ROUTE OF ADMINISTRATION: IV(Chemoport)

80. DRUGS AND REGIME USED: ANTHRACYCLINES: ꞏ Anthracyclines are first line drugs ꞏDaunorubicin, Doxorubicin, Adriamycin, Epirubicin. ꞏCardiotoxicity can develop as late as more than one year post-chemotherapy period.

81. TAXANES : ꞏ Taxanes are 2nd line drugs. ꞏ Paclitaxel, Docetaxel ꞏ Used sequentially or concurrently with anthracyclines ꞏ Used commonly for locally advanced (LABC) and metastatic breast cancer (MSC) REGIME AVAILABLE: CAF CEF CMF TAC\AC Cyclophosphamide Cyclophosphamide Cyclophosphamide Taxanes(docetaxel/ paclitaxel Adriamycin Epirubicin Methotrexate Adriamycin 5-Flurouracil 5-Flurouracil 5-Flurouracil Cyclophosphamide

82. TARGETED THERAPY: DRUGS : Trastuzumab(Herceptin) Pertuzumab USES: only in HER-2/Neu positive cancers. DOSE: 4 mg/kg as loading; 2 mg/kg as maintenance for 1 year. G given as intravenous infusion. REGIME FOR HER-2/NEU POSITIVE CANCERS: 1.Trastuzumab+Docetaxel 2.Pertuzumab+Docetaxel 3.Pertuzumab+Trastuzumab 4.Pertuzumab+Trastuzumab+Docetaxel

83. HORMONE THERAPY: Includes: Oestrogen receptor antagonists[SERM]- tamoxifen. Oral aromatase inhibitors - Letrozole. Ovarian ablation by surgery (Bilateral oophorectomy) or by radiation. Progesterone receptor antagonist

84. HORMONE THERAPY TAMOXIFEN: ꞏ It is an SERM ꞏ Dose is 20 mg OD for 5 years, 10years In high risk patients(node positive, tumor >5 cm) ꞏ Half life of tamoxifen is 7 days; it takes 4 weeks to show its benefits Adverse effects: Nausea , weight gain, hot flushes, vaginal bleeding, bone pain, amenorrhea It is presently used for premenopausal women .

85. HORMONE THERAPY LETROZOLE: ꞏ It is an aromatase inhibitor ꞏ It is used as in postmenopausal women . ꞏ Dosage of letrozole is 2.5 mg once daily. ꞏ It is given for 5 years (or) for 2 years following 3 years of tamoxifen. ADVERSE EFFECTS: Osteoporosis, Vaginal dryness, hot flushes, vaginal bleeding, cardiovascular problem

86. TREATMENT Neoadjuvant chemotherapy Responders Non-responders Surgery Chemotherapy Hormonal therapy Progressive disease