Evaluation and Management of Carcinoma Breast

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Information about Evaluation and Management of Carcinoma Breast

Published on November 2, 2016

Author: dpsanand

Source: slideshare.net

1. Presented by: Dr. Davinder Pal Singh 1

2. Functional Anatomy of Breast  Modified sweat gland-modified apocrine gland  Made up of 15–20 lobules of glandular tissue embedded in fat.  Fat accounts for its smooth contour and most of its bulk.  These lobules are separated by fibrous septa running from the subcutaneous tissues to the fascia of the chest wall (the ligaments of Cooper/ Astley Cooper fibers/ suspensory ligaments)

3. Functional Anatomy  The mature female breast extends from the level of second or third rib to the inframammary fold at sixth or seventh rib.  It extends transversely from the lateral border of the sternum to the mid-axillary line.  The deep or posterior surface of the breast rests on the fascia of the pectoralis major, serratus anterior, external oblique abdominal muscle and the upper extent of the rectus sheath  The axillary tail pierces the fascia and lies in the axilla 3

4. Anatomy  Each lobule drains by its lactiferous duct on to the nipple, which is surrounded by the pigmented areola.  This area is lubricated by the areolar glands of Montgomery  large,  modified sebaceous glands →may form sebaceous cysts → may infected.

5. Surface anatomy

6. Naming the quadrants for the purpose of describing a lump  Or 1. Upper medial quadrant 2. Upper lateral quadrant 3. Lower medial quadrant 4. Lower lateral quadrant

7. Blood Supply  The breast receives its principal blood supply from:  (a) perforating branches of the internal mammary artery;  (b) lateral branches of the posterior intercostal arteries; and  (c) branches from the axillary artery, including the highest thoracic, lateral thoracic, and pectoral branches of the thoraco-acromial artery

8. Venous drainage  The veins of the breast and chest wall follow the course of the arteries, with venous drainage being toward the axilla.  The three principal groups of veins are:  (a) Perforating branches of the internal thoracic vein,  (b) Perforating branches of the posterior intercostal veins,  (c) Tributaries of the axillary vein.

9.  Batson’s vertebral venous plexus, which invests the vertebrae and extends from the base of the skull to the sacrum, may provide a route for breast cancer metastases to the:  vertebrae, skull, pelvic bones, and central nervous system. 12

10. Lymphatic drainage

11. Lymphatic Drainage  Anterior (pectoral) group: Lying along the lower border of the pectoralis minor behind the pectoralis major, these nodes receive lymph vessels from the lateral quadrants of the breast and superficial vessels from the anterolateral abdominal wall above the level of the umbilicus.  Posterior (subscapular) group: Lying in front of the subscapularis muscle, these nodes receive superficial lymph vessels from the back, down as far as the level of the iliac crests.  Lateral group: Lying along the medial side of the axillary vein, these nodes receive most of the lymph vessels of the upper limb (except those superficial vessels draining the lateral side).

12.  Central group: Lying in the center of the axilla in the axillary fat, these nodes receive lymph from the above three groups.  Infraclavicular (deltopectoral) group: These nodes are not strictly axillary nodes because they are located outside the axilla. They lie in the groove between the deltoid and pectoralis major muscles and receive superficial lymph vessels from the lateral side of the hand, forearm, and arm.  Apical group: Lying at the apex of the axilla at the lateral border of the 1st rib, these nodes receive the efferent lymph vessels from all the other axillary nodes. 16

13.  A sub-areolar plexus of lymphatics below the nipple (the plexus of Sappey)  DRAINAGE  75% → axillary  15% → internal mammary  Upper → can go to supraclavicular  Lower 2 quadrants can go to subdiapragmatic or abdominal nodes

14. Lymph Nodes - Levels  The lymph node groups are assigned levels according to their anatomic relationship to the pectoralis minor muscle.  Lymph nodes located lateral to or below the lower border of the pectoralis minor muscle are referred to as level I lymph nodes, which include the anterior, posterior, and lateral groups.  Lymph nodes located superficial or deep to the pectoralis minor muscle are referred to as level II lymph nodes, which include the central and interpectoral groups.  Lymph nodes located medial to or above the upper border of the pectoralis minor muscle are referred to as level III lymph nodes, which consist of the apical group. 19

15. 20 The lymph node groups are assigned levels according to their anatomic relationship to the pectoralis minor muscle

16. Nerve Supply  Lateral cutaneous branches of the third through sixth inter- costal nerves provide sensory innervation of the breast (lateral mammary branches) and of the anterolateral chest wall.  These branches exit the intercostal spaces between slips of the serratus anterior muscle.  Cutaneous branches that arise from the cervical plexus, specifically the anterior branches of the supraclavicular nerve, supply a limited area of skin over the upper portion of the breast. 22

17. Development and structure  Begins to develop as early as the 4th week as a downgrowth from a thickened mammary ridge (milk line) of ectoderm along a line from the axilla to the inguinal region.  Supernumerary nipples or even glands proper may form at lower levels on this line.  Lobule formation occurs only in the female breast & does so after puberty.  Each lactiferous duct is connected to a tree-like system of ducts and lobules, intermingled & enclosed by connective tissue to form a lobe of the gland.

18.  The resting (non-lactating) breast, however consists mostly of fibrous & fatty tissue; variations in size are due to variations in fat content, not glandular tissue which is very sparse.  During pregnancy alveoli bud off from the smaller ducts & the organ usually enlarges significantly, & more so in preparation for lactation.  When lactation ceases there is involution of secretory tissue.  After menopause progressive atrophy of lobes & ducts takes place.

19. 26

20. Epidemiology  Breast cancer is the most common site-specific cancer in women and is the leading cause of death from cancer for women aged 20 to 59 years.  It accounts for 29% of all newly diagnosed cancers in females and is responsible for 14% of the cancer related deaths in women.  Breast cancer was the leading cause of cancer-related mortality in women until 1987, when it was surpassed by lung cancer. 27

21. Risk factors  Alcohol and smoking.  Obesity  Late first pregnancy (usually after 30 years) – Elder primigravida  Age at first full time pregnancy: early the pregnancy, more it will be protective  Oral contraceptives and Hormone replacement therapies  Nuliparity  Breastfeeding is protective  Early menarche and late menopause  Genetic factors : BRCAI and BRCAII positive, positive family history, personal history 28

22. Site of Metastasis  Common sites of involvement, in order of frequency, are bone, lung, pleura, soft tissues, and liver.  Brain metastases are less frequent overall although with the advent of adjuvant systemic therapies it has been reported that CNS disease may be seen earlier.  There are also reports of factors which are associated with the risk of developing brain metastases.  For example, they are more likely to be seen in patients with triple receptor negative breast cancer (ER-negative, PR-negative and HER2-negative) or patients with HER2- positive breast cancer who have received chemotherapy and HER2-directed therapies. 29

23. Histopathology of Breast Cancer  Cancer cells are in situ or invasive depending on whether or not they invade through the basement membrane.  Broders’s original description of in situ breast cancer stressed the absence of invasion of cells into the surrounding stroma and their confinement within natural ductal and alveolar boundaries.  Because areas of invasion may be minute, the accurate diagnosis of in situ cancer necessitates the analysis of multiple microscopic sections to exclude invasion. 30

24.  Carcinoma-in-situ mostly includes: Ductal carcinoma in situ (DCIS) and Lobular carcinoma in situ (LCIS)  When screening mammography became popular, a 14- fold increase in the incidence of in situ cancer (45%) was demonstrated, and DCIS was more frequently diagnosed than LCIS by a ratio of >2:1. 31

25. 32

26.  Multicentricity refers to the occurrence of a second breast cancer outside the breast quadrant of the primary cancer (or at least 4 cm away), whereas  Multifocality refers to the occurrence of a second cancer within the same breast quadrant as the primary cancer (or within 4 cm of it). 33

27. Invasive Breast Cancer  Invasive breast cancers have been described as lobular or ductal in origin.  Early classifications used the term lobular to describe invasive cancers that were associated with LCIS, whereas all other invasive cancers were referred to as ductal.  Current histologic classifications recognize special types of breast cancers (10% of total cases), which are defined by specific histologic features. 34

28.  To qualify as a special-type cancer, at least 90% of the cancer must contain the defining histologic features.  About 80% of invasive breast cancers are described as invasive ductal carcinoma of no special type (NST).  These cancers generally have a worse prognosis than special-type cancers. 35

29.  Foote and Stewart originally proposed the following classification for invasive breast cancer:  Paget’s disease of the nipple  Invasive ductal carcinoma—Adenocarcinoma with productive fibrosis (scirrhous, simplex, NST), 80%  Medullary carcinoma, 4%  Mucinous (colloid) carcinoma, 2%  Papillary carcinoma, 2%  Tubular carcinoma, 2%  Invasive lobular carcinoma, 10%  Rare cancers (adenoid cystic, squamous cell, apocrine) 36

30. Diagnosis of Breast cancer  In~30% of cases, the woman discovers a lump in her breast. Other less frequent presenting signs and symptoms of breast cancer include:  (a) breast enlargement or asymmetry;  (b) nipple changes, retraction, or discharge;  (c) ulceration or erythema of the skin of the breast;  (d) an axillary mass; and  (e) musculoskeletal discomfort.  However, up to 50% of women presenting with breast complaints have no physical signs of breast pathology.  Breast pain usually is associated with benign disease. 37

31. Triple Assessment  Clinical examination  Imaging (usually mammography, ultrasonography or both, MR Mammography has been recently added)  Needle biopsy : Tru-cut biopsy (Histologic evidence)  Triple assessment is a very useful diagnostic tool to evaluate patients with breast lumps and to detect patients with breast cancers with an overall accuracy of 99.3%.  Triple assessment was useful in diagnosing breast cancers at an earlier stage, with most of breast cancers detected at stage I or stage II ( T1 or T2 : N0 or N1, M0). 38

32. Examination  Inspection: The surgeon inspects the woman’s breast with her arms by her side, with her arms straight up in the air, and with her hands on her hips (with and without pectoral muscle contraction).  Symmetry, size, and shape of the breast are recorded, as well as any evidence of edema (Peaud’ orange), nipple or skin retraction, or erythema.  With the arms extended forward and in a sitting position, the woman leans forward to accentuate any skin retraction. SR_Ca_Breast_Rx 39

33. Examination  Palpation: As part of the physical examination, the breast is carefully palpated.  With the patient in the supine position the surgeon gently palpates the breasts, making certain to examine all quadrants of the breast from the sternum laterally to the latissimus dorsi muscle and from the clavicle inferiorly to the upper rectus sheath. 40

34.  A systematic search for lymphadenopathy then is performed.  Following figure shows the position of the patient for examination of the axilla. 41 A. Inspection of the breast with arms at sides. B. Inspection of the breast with arms raised. C. Palpation of the breast with the patient supine. D. Palpation of the axilla.

35. Imaging Techniques  Mammography. Mammography has been used in North America since the 1960s, and the techniques used continue to be modified and improved to enhance image quality.  Conventional mammography delivers a radiation dose of 0.1 cGy per study.  By comparison, chest radiography delivers 25% of this dose.  However, there is no increased breast cancer risk associated with the radiation dose delivered with screening mammography. 42

36. Screening Mammography  Screening mammography is used to detect unexpected breast cancer in asymptomatic women. In this regard, it supplements history taking and physical examination.  With screening mammography, two views of the breast are obtained, the craniocaudal (CC) view and the mediolateral oblique (MLO) view.  The MLO view images the greatest volume of breast tissue, including the upper outer quadrant and the axillary tail of Spence.  Compared with the MLO view, the CC view provides better visualization of the medial aspect of the breast and permits greater breast compression. 43

37. Diagnostic Mammography  Diagnostic mammography is used to evaluate women with abnormal findings such as a breast mass or nipple discharge.  In addition to the MLO and CC views, a diagnostic examination may use views that better define the nature of any abnormalities, such as the 90-degree lateral and spot compression views.  The 90-degree lateral view is used along with the CC view to triangulate the exact location of an abnormality. 44

38. 45 Premenopausal Mammogram

39. 46 Post menopausal Mammogram

40. Ductography  Ductography: The primary indication for ductography is nipple discharge, particularly when the fluid contains blood.  It is not commonly used  Radiopaque contrast media is injected into one or more of the major ducts and mammography is performed.  With the patient in a supine position, 0.1 to 0.2 mL of dilute contrast media is injected and CC and MLO mammographic views are obtained without compression.  Intraductal papillomas are seen as small filling defects surrounded by contrast media.  Cancers may appear as irregular masses or as multiple intraluminal filling defects. 47

41. USG  Ultrasonography: It is usually done in <35 years of age. Second only to mammography in frequency of use for breast imaging, ultrasonography is an important method of resolving equivocal mammographic findings, defining cystic masses, and demonstrating the echogenic qualities of specific solid abnormalities.  Benign breast masses usually show smooth contours, round or oval shapes, weak internal echoes, and well- defined anterior and posterior margins.  Breast cancer characteristically has irregular walls but may have smooth margins with acoustic enhancement.  Its findings are highly reproducible and it has a high patient acceptance rate, but it does not reliably detect lesions that are ≤1 cm in diameter. 48

42.  Ultrasonography can also be utilized to image the regional lymph nodes in patients with breast cancer.  The sensitivity of examination for the status of axillary nodes ranges from 35% to 82% and specificity ranges from 73% to 97%.  The features of a lymph node involved with cancer include cortical thickening, change in shape of the node to more circular appearance, size larger than 10 mm, absence of a fatty hilum and hypoechoic internal echoes. 49

43. MRI  There is current interest in the use of MRI to screen the breasts of high-risk women and of women with a newly diagnosed breast cancer.  MRI can also detect additional tumors in the index breast (multifocal or multicentric disease) that may be missed on routine breast imaging and this may alter surgical decision making . 50

44.  Some clinical scenarios where MRI may be useful include:  The evaluation of a patient who presents with nodal metastasis from breast cancer without an identifiable primary tumor;  To assess response to therapy in the setting of neoadjuvant systemic treatment;  To select patients for partial breast irradiation techniques; and  Evaluation of the treated breast for tumor recurrence. 51

45. Breast Biopsy  Nonpalpable Lesions: Image-guided breast biopsy specimens are frequently required to diagnose nonpalpable lesions.  Ultrasound localization techniques are used when a mass is present, whereas stereotactic techniques are used when no mass is present (microcalcifications or architectural distortion only).  However, although FNA biopsy permits cytologic evaluation, core-needle permits the analysis of breast tissue architecture and allows the pathologist to determine whether invasive cancer is present.  This permits the surgeon and patient to discuss the specific management of a breast cancer before therapy begins. 52

46.  Core-needle biopsy is preferred over open biopsy for nonpalpable breast lesions because a single surgical procedure can be planned based on the results of the core biopsy and tissue for receptor status evaluation like ER/PR; Her2/Neu.  The advantages of core-needle biopsy include a low complication rate, minimal scarring, and a lower cost compared with excisional breast biopsy. 53

47.  Palpable Lesions. FNA or core biopsy of a palpable breast mass can usually be performed in an outpatient setting.  A 1.5-in, 22-gauge needle attached to a 10-mL syringe or a 14 gauge core biopsy needle is used.  For FNA, use of a syringe holder enables the surgeon performing the FNA biopsy to control the syringe and needle with one hand while positioning the breast mass with the opposite hand.  After the needle is placed in the mass, suction is applied while the needle is moved back and forth within the mass.  Once cellular material is seen at the hub of the needle, the suction is released and the needle is withdrawn. 54

48.  The cellular material is then expressed onto microscope slides. Both air-dried and 95% ethanol– fixed microscopic sections are prepared for analysis.  When a breast mass is clinically and mammographically suspicious, the sensitivity and specificity of FNA biopsy approaches 100%. 55

49. Live Tissue Sampling  Recently live tissue samples from surgery are tested with various chemotherapy agents to derive probabilities of which ones may work better and especially the ones which would not work (cell-death assays).  The companies need the sample within 24 hours of surgical excision.  This is especially useful for early stage cancers where a response for the therapy cannot be determined once the whole cancer is taken out during the surgery and the chemotherapy is given in an adjuvant setting.  However, the benefits of such tests have not yet been established in clinical trials and is not mainstream. 56

50. Breast Cancer Staging  A frequently used staging system is the TNM (tumor, nodes, and metastasis) system.  The American Joint Committee on Cancer (AJCC) has modified the TNM system for breast cancer 57

51. 58 Early Breast Cancer(EBC): Stage I & II, T1N1M0, T2N1M0, Operable T3N0M0 Locally Advanced Breast Cancer(LABC): Stage IIIA & IIIB Metastatic Breast Cancer: Stage IV

52. Early Carcinoma Breast  Lesions included in this category: T2N1M0  However nowadays: Operable T3N1M0 lesions are also included 59

53. Management: Early Carcinoma Breast  There are usually two options:  Breast Conservation Surgery (BCS)  Modified Radical Mastectomy (MRM) 60

54. Breast Conservation Surgery  Breast conservation surgery involves “Wide local excision” of the breast lump and then followed by “Axillary clearance”, if Sentinel lymph node biopsy comes out to be positive.  Usually done in lumps up to the size of 4 cm.  Normal tissue rim which is removed around the tumor is 0.5 to 1 cm.  “A minimum rim of 2mm is considered optimum”-ACS Surgery: Principles and Practice 61

55. Contraindications of BCS  Multifocal disease  Prior history Radiotherapy  Pregnancy  Pulmonary Tuberculosis  Inability to achieve negative margin  Active connective tissue disorders : Collagen disorders, Scleroderma  Tumor size > 5 cm  The patient lives in an area where radiotherapy is inaccessible  The patient is apprehensive about the risk of local recurrence after lumpectomy 62

56.  Large tumor:: Breast Ratio  Familial Carcinoma Breast : BRCAI and BRCA II 63

57. Sentinel Lymph Node Biopsy  A sentinel lymph node is defined as the first lymph node to which cancer cells are most likely to spread from a primary tumor.  Sometimes, there can be more than one sentinel lymph nodes.  Currently, the American Society of Clinical Oncology recommends that a positive SLN should be routinely followed by completion ALND. 64

58. SLN Biopsy Technique  First introduced for lymphatic mapping and SLN biopsy in treatment of melanoma, then same techniques was subsequently applied to breast cancer.  Radioactive Sulphur Colloid is used: Technetium-99m (Tc99) sulphur colloid.  Site: Intra-tumor injection, Peritumor.  The accuracy of identifying the SLNs of the breast is enchanced by combining the injection of isosulfan blue with radioactive sulphur colloid. 65

59. 66 Visualization of blue-stained lymphatic traveling to the blue-stained sentinel node.

60. 67 Visualization of the blue- stained lymphatic traveling to the unstained sentinel node.

61. Wide Local Excision  BCS is generally performed by making a skin incision above the tumor to avoid tunneling.  After making the skin incision, the skin and subcutaneous fat are dissected off the breast lump.  When elevating skin, it is important not to disrupt the subcutaneous fat as thin skin flaps give a poor cosmetic result.  The skin flaps should be elevated 1 to 2 cm beyond the edge of the cancer.  The fingers of the non-dominant hand are then placed over the palpable cancer and the breast tissue divided beyond the fingertips; 68

62. Technique  The line of incision should be 1 cm beyond the limit of the palpable mass.  Having divided breast tissue beyond the edge of the cancer, the deep aspect of the tumor can be palpated and breast tissue under the cancer divided.  It is usually but not always necessary to remove full thickness of breast tissue.  To ensure that there is an adequate margin deep to the cancer, for the majority of patients dissection through the breast tissue is continued down to the pectoral fascia and the breast tissue containing the cancer is lifted off the pectoral fascia.  It is not necessary to excise pectoral fascia unless it is tethered to the tumor. 69

63. Technique  If a carcinoma is infiltrating one of the chest wall muscles, then a portion of the affected muscle should be removed beneath the tumor in order to excise tissue beyond the limits of the cancer.  For very superficial cancers in parts of the breast with significant depth, it is possible to clear the deep margins without removing the full thickness of the breast. 70

64.  Having lifted the tumor and surrounding breast tissue of the chest wall muscles, the cancer and surrounding tissue are grasped between the finger and the thumb of the non-dominant hand and excision is completed at the other margins  The specimen is immediately orientated prior to submission to the pathologist with sutures, ligaclips, or metal markers. 71

65. 72 Finger of non-dominant hand is placed over palpable cancer and breast tissue is divided beyond the fingertips.

66. 73 After having dissected around three sides of the cancer, it is grasped with finger and thumb of the non-dominant hand before completing the excision at the other margins.

67.  Using metal markers or ligaclips has the advantage of allowing orientated anteroposterior-intraoperative specimen radiography to be performed.  This helps the surgeon to determine that the target lesion has been excised and permits assessment of the completeness of excision at radial margins.  If the specimen radiograph shows that the cancer or any associated micro-calcification is close to a radial margin, then the surgeon can remove further tissue from the margin of concern, orientate this tissue, and send it for pathologic evaluation 74

68. 75 Orientation of the specimen: In our unit, we use skin threads for marking

69. Technique  Having excised the cancer from the breast, suturing the defect in the breast without mobilization of the breast tissue usually results in distortion of the breast contour.  Small defects (<5% breast volume) in subcutaneous tissue can be left open and can produce a good final cosmetic result, however the skin incision should be closed.  Larger defects in the breast should be closed by mobilizing the surrounding breast tissue from both the overlying skin and subcutaneous tissue and the underlying chest wall. 76

70.  If large defects (>10% breast volume) are not closed, they fill with seroma, which later absorbs; as scar tissue forms, this contracts, often producing an ugly, distorted breast.  The extent to which breast tissue can be mobilized depends on its density and type.  Soft fatty breast tissue cannot be mobilized widely as its blood supply is such that tissues at the edges of the excision undergo fat necrosis and produce a very poor final cosmetic result.  In contrast, dense fibrous breast tissue can be mobilized widely to fill defects and heals well. 77

71.  Following large-volume excisions, having mobilized breast tissue, it is usually possible to close the defect in the breastplate with a series of interrupted absorbable sutures.  Larger defects can be filled by using a latissimus dorsi muscle miniflap, local flaps, or more major breast reshaping as part of a unilateral or bilateral therapeutic mammoplasty.  Drains are not necessary following wide local excision and should not be used routinely.  They do not protect against hematoma formation and increase in infection rates. 78

72.  Breast skin wounds should be closed in layers with absorbable sutures, finishing with a subcuticular suture.  Local anesthetic, usually a combination of bupivacaine and adrenaline, infiltrated into the wound reduces postoperative pain. 79

73. Axillary Dissection: Technique  Exposure is facilitated by placing a wedge or sandbag under the ipsilateral shoulder so as to elevate the axilla.  The ipsilateral arm should be prepared and draped separately so that the arm can be moved above the patient’s head.  The skin of the arm up to and above the elbow is prepared and the lower arm and hand are wrapped in a sterile drape and secured with a stockinette. 80

74. 81 The ipsilateral elbow is flexed and the arm is moved over the patient’s head to facilitate retraction of pectoral muscles and exposure of the axilla.

75.  A skin crease incision just distal to the pectoralis major muscle is easily palpable and dissection should continue to it.  If the procedure is being performed through a transverse incision, then the next stage in the procedure is to elevate the skin laterally off the underlying structures down to the edge off the latissimus dorsi muscle.  Having identified the latissimus dorsi muscle, attention is then transferred back to the medial part of the dissection and the lateral border of the pectoralis major muscle is dissected superiorly and inferiorly.  At this point, retractors replace skin hooks and the pectoralis minor muscle is identified and its lateral edge is carefully cleared. 82

76.  Care is taken to identify and preserve the medial pectoral nerve and vessels that pass into the lateral border of the pectoralis minor muscle: these innervate both the pectoralis minor and the lower lateral third of the pectoralis major muscle.  While retracting the pectoralis major and minor muscles, the elbow is bent and the arm moved upward behind the patient’s head . This makes retraction of the pectoral muscles easier.  Care must be taken when the arm is retracted not to overstretch the brachial plexus.  With the pectoralis major and minor muscles retracted medially, by an assistant, it is possible to identify the nodes under the pectoralis minor muscle. 83

77. 84 Incisions for axillary dissection. A: Skin crease incision distal to the hair- bearing skin of the axilla. (This is usually preferred in our unit) B: Lazy S incision placed between pectoralis major and latissimus dorsi muscles. C: Anterior axillary fold incision (dashed line) placed parallel and posterior to lateral border of the pectoralis major muscle.

78.  Beyond the medial margin of the pectoralis minor muscle and covered by the stretched clavipectoral fascia lies a small conical depression adipose tissue containing a small number of lymph nodes.  The upper limit of this depression is defined by the axillary vein where it meets the subclavius muscle tendon, which forms its medial limit.  Nodes in this adipose tissue comprise the third axillary level, as described by Berg.  There remains conflict as to what comprises an adequate axillary clearance.  Some surgeons perform a level I/II dissection, others remove levels I and II, and some remove all nodes to level III routinely.  An empirical approach based on the findings at operation seems reasonable. 85

79.  The dissection then continues underneath the pectoralis minor muscle to remove the level II nodes.  The inferior flap is dissected down to the axillary tail of the breast and carried to the serratus anterior fascia inferiorly and the latissimus dorsi muscle posteriorly.  The edge of the latissimus dorsi muscle defines the lateral border of dissection.  The intercostobrachial nerve traverses the axilla and passes across the lateral edge of the latissimus dorsi muscle and can be damaged if the lateral edge of the latissimus dorsi muscle is dissected up to the level of the axillary vein, so the lateral dissection should not be performed until this nerve has been identified. 86

80. 87 Major neurovascular structures to be preserved in an axillary clearance/dissection.

81.  By this point of the operation, the medial border, the entire inferior border, and the lower half of the lateral border have been defined.  The next step is to develop dissection from medial to lateral by a combination of sharp and blunt dissection and clear the tissue inferior to the central part of the axillary vein.  The lower border of the axillary vein represents the superior limit of the dissection.  The tissue below the axillary vein is dissected from the vein all the way to the edge of the latissimus dorsi muscle.  Veins that drain into the axillary vein on its anterior surface are divided between ties or ligaclips. 88

82.  The fat and lymph nodes are teased away from the chest wall by blunt dissection and the intercostobrachial nerve is identified leaving the chest wall.  This is usually in the second intercostal space but can be in the first.  Dissecting out the whole of this nerve as it courses across the axilla can be tedious but it is worthwhile as it avoids the annoying numbness and occasionally pain or hyperesthesia that affects the skin of the upper inner arm that develops when this nerve has been divided. 89

83.  Once this nerve (intercostobrachial) is identified passing across the axilla and dissected from surrounding structures, it can be retracted superiorly.  The next step is to identify and preserve the long thoracic nerve.  This nerve can be identified by retracting the axillary contents laterally.  It has a tendency to be pulled out laterally with these contents and it is situated approximately 2 cm posterior to the intercostobrachial nerve.  Blunt dissection in the valley between the serratus anterior muscle and the axillary contents usually identifies this nerve. 90

84.  Once it has been identified, it is freed and pushed back toward the chest wall and preserved.  Certain identification and protection of this nerve is one of the most important principles in this operation.  Dissection along the lower border of the axillary vein continues in a medial-to-lateral direction.  The next structures to be identified are the thoracodorsal nerve and vessels.  The thoracodorsal vessels are situated about two-thirds of the way across the axilla from medial to lateral.  The vein is often the first structure to be identified as it drains into the posterior aspect of the axillary vein; the nerve is the most medial structure of this neurovascular bundle. 91

85.  Having identified and protected these vessels, the valley on the subscapularis muscle between the long thoracic and thoracodorsal nerves are cleaned with a cranial-to-caudal dissection. As the fat, lymphatic vessels, and blood vessels pass underneath the axillary vein the structures are divided between artery forceps or liga-clips.  The dissection then continues inferiorly, and branches passing from the thoracodorsal vessels into the axillary fat are identified;  Dissection continues laterally, removing tissue lateral to and behind the thoracodorsal vessels to the lateral margin of the latissimus dorsi muscle.  This allows completion of the lateral part of the operation. 92

86.  The thoracodorsal vessels and the long thoracic nerves are left in the axilla while the axillary nodes and fat are retracted anteriorly.  The inferior margin of the dissection is completed by dividing the axillary tail of the breast under direct vision.  Any vessels passing into the tail of the breast are diathermied or ligated.  The wound is irrigated with either savlon or sterile water, and hemostasis is secured.  A single suction drain is placed into the cavity and brought out through a separate stab incision.  If possible, the skin flaps are sutured to the chest wall as results from small trials of axillary quilting have shown a decrease in subsequent seroma rate.  Finally, the wound is closed in layers with absorbable sutures before infiltration with local anesthetic. 93

87. SR_Ca_Breast_Rx 94

88. Modified Radical Mastectomy  The contraindications of BCS becomes indications for MRM.  The operation was first described by David Patey.  Anatomic boundaries of the modified radical mastectomy are the anterior margin of the latissimus dorsi muscle laterally, the midline of the sternum medially, the subclavius muscle superiorly, and the caudal extension of the breast 2 to 3 cm inferior to the inframammary fold inferiorly. 95

89. M.R.M: Surgical Technique  The more recently utilized mastectomy is the skin- sparing mastectomy, which removes all breast tissue, the nipple–areola complex, and only 1 cm of skin around excised scars.  There is a recurrence rate of less than 2% to 4% when skin-sparing mastectomy is used for T1 to T3 cancers. 96

90.  A total(simple)mastectomy removes all breast tissue, the nipple–areola complex, and necessary skin.  An extended simple mastectomy removes all breast tissue, the nipple–areola complex, necessary skin, and the level I axillary lymph nodes.  The modified radical mastectomy removes all breast tissue, the nipple–areola complex, necessary skin, and the level I and II axillary lymph nodes.  The Patey’s modification of the modified radical mastectomy also removes the pectoralis minor muscle, which permits complete dissection of the apical (level III) axillary lymph nodes.  The Halsted radical mastectomy removes all breast tissue, the nipple–areola complex, necessary skin, the pectoralis major and pectoralis minor muscles, and the level I, II, and III axillary lymph nodes.  Currently, chemotherapy, hormone therapy, and radiation therapy for breast cancer have nearly eliminated the need for a Halsted RM 97

91. Variants of MRM  Important Variants of MRM include: Scanlon’s Operation: Pectoralis minor incised Level III LN removed Madden and Auchincloss’ MRM: Pectoralis minor left intact, Level I and II lymph node dissection is done. Level III LN not removed, Reduced arm swelling and high chance of pectoral nerve preservation 98

92. Technique  A modified radical mastectomy preserves the pectoralis major muscle with removal of level I, II, and III (apical) axillary lymph nodes.  The operation was first described by David Patey, a surgeon at St Bartholomew’s Hospital London, who reported a series of cases where he had removed the pectoralis minor muscle allowing complete dissection of the level III axillary lymph nodes while preserving the pectoralis major and the lateral pectoral nerve.  A modified radical mastectomy permits preservation of the medial (anterior thoracic) pectoral nerve, which courses in the lateral neurovascular bundle of the axilla and usually penetrates the pectoralis minor to supply the lateral border of the pectoralis major. 99

93.  Anatomic boundaries of the modified radical mastectomy are:  the anterior margin of the latissimus dorsi muscle laterally,  the midline of the sternum medially,  the subclavius muscle superiorly, and  the caudal extension of the breast 2 to 3 cm inferior to the inframammary fold inferiorly.  Skin-flap thickness varies with body habitus but ideally is 7 to 8 mm inclusive of skin and tela subcutanea.  Once the skin flaps are fully developed, the fascia of the pectoralis major muscle and the overlying breast tissue are elevated off the underlying musculature, which allows for the complete removal of the breast. 100

94.  Subsequently, an axillary lymph node dissection is performed.  The most lateral extent of the axillary vein is identified and the areolar tissue of the lateral axillary space is elevated as the vein is cleared on its anterior and inferior surfaces.  The areolar tissues at the junction of the axillary vein and the anterior edge of the latissimus dorsi muscle, which include the lateral and subscapular lymph node groups (level I), are cleared.  Care is taken to preserve the thoracodorsal neurovascular bundle. 101

95.  The dissection then continues medially with clearance of the central axillary lymph node group (level II).  The long thoracic nerve of Bell is identified and preserved as it travels in the investing fascia of the serratus anterior muscle.  Every effort is made to preserve this nerve, because permanent disability with a winged scapula and shoulder weakness will follow denervation of the serratus anterior muscle.  Patey divided the pectoralis minor and removed it to allow access right up to the apex of the axilla. The pectoralis minor muscle is usually divided at the tendinous portion near its insertion onto the coracoid process, which allows dissection of the axillary vein medially to the costo-clavicular (Halsted’s) ligament.  Finally, the breast and axillary contents are removed from the surgical bed and are sent for pathologic assessment. 102

96.  In Patey’s modified radical mastectomy he removed the pectoralis minor muscle.  Many surgeons now divide only the tendon of the pectoralis minor muscle at its insertion onto the coracoid process while leaving the rest of the muscle intact, which still provides good access to the apex of the axilla.  Seromas beneath the skin flaps or in the axilla represent the most frequent complication of mastectomy and axillary lymph node dissection, reportedly occurring in as many as 30% of cases.  The use of closed-system suction drainage reduces the incidence of this complication.  Catheters are retained in the wound until drainage diminishes to <30 mL per day.  Wound infections occur infrequently after a mastectomy and the majority are a result of skin-flap necrosis. 103

97.  The incidence of functionally significant lymphedema after a modified radical mastectomy is approximately 20% but can be as high as 50% to 60% when postoperative radiation is employed.  Extensive axillary lymph node dissection, the delivery of radiation therapy, the presence of pathologic lymph nodes, and obesity are predisposing factors.  Patients should be referred to physical therapy at the earliest signs of lymphedema to prevent progression to the later stages.  The use of individually fitted compressive sleeves and complex decongestive therapy may be necessary. 104

98. 105

99. COMPLICATIONS of M.R.M/MASTECTOMY  Injury/ Thrombosis of Axillary Vein  Seroma  Shoulder Dysfunction  Pain and Numbness  Flap Necrosis and infection  Lymphoedema and its problems  Axillary hyperaesthesia  Winged Scapula 106

100. Locally Advanced Breast Carcinoma (LABC)  Included here are the tumor with stage: T3/4N2M0.  In these cases, first of all the downstaging of the tumor is initially performed, then after 2 or 3 cycles of NACT, the tumor is reevaluated.  If the response is considered adequate, then the surgery is undertaken, if the tumor becomes resectable either via MRM/BCS 107

101.  However, newer guidelines:  “MRM can be attempted in cases of LABC”- Surgical Update 2016, MAMC, New Delhi. 108

102. Metastatic Breast Carcinoma  Treatment for stage IV breast cancer is not curative but may prolong survival and enhance a woman’s quality of life.  Endocrine therapies that are associated with minimal toxicity are preferred to cytotoxic chemotherapy in estrogen receptor positive disease.  Systemic chemotherapy is indicated for women with hormone receptor-negative cancers  Women with stage IV breast cancer may develop anatomically localized problems that will benefit from individualized surgical or radiation treatment, such as brain metastases, pleural effusion, impending or existing pathologic fracture of a long bone, spinal cord compression, and painful bone or soft tissue metastases. 109

103. LYMPHANGIOSARCOMA (Stewart- Treve’s Syndrome) In ipsilateral upper limb Develops in people with Lymphoedema after Mastectomy with Axillary clearance. 3-5 years after development of Lymphoedema Presentation: Multiple subcutaneous nodules Requires Forequarter Amputation Poor prognosis 110

104. RADIOTHERAPY Radiation treatment is mainly effective in reducing the risk of local relapse in the affected breast. Therefore, it is recommended in most cases of breast conserving surgeries and less frequently after mastectomy. Indications for radiation treatment are constantly evolving. Radiation therapy is usually recommended for all patients who had lumpectomy, quadrant-resection. Radiation therapy is usually not indicated in patients with advanced (stage IV disease) except for palliation of symptoms like bone pain or fungating lesions. 111

105. Recommendation In general recommendations would include radiation:  As part of breast conserving therapy.  After mastectomy for patients with higher risk of recurrence because of conditions such as a large primary tumor or substantial involvement of the lymph nodes. Other factors which may influence adding adjuvant radiation therapy:  Tumor close to or involving the margins on pathology specimen  Multiple areas of tumor (multicentric disease)  Microscopic invasion of lymphatic or vascular tissues  Microscopic invasion of the skin, nipple/areola, or underlying pectoralis major muscle  Patients with extension out of the substance of a LN  Inadequate numbers of axillary LN sampled 112

106. Chest Wall Axilla Post-BCS T3 tumour>5cm Residual disease LABC Positive margin/close surgical margin <2cm Conservative surgery Inflammatory Carcinoma >4 nodes +’ve Extra-nodal spread Axillary status unknown/ not assessed MANDATORY! Local + Axilla Tangential fields: 50 Gy- 25 fractions-5 weeks Another 10 Gy to tumour bed Internal Mammary and Supra-clavicular area may be included in the radiation field SR_Ca_Breast_Rx 113

107. HORMONE-THERAPY Approach Principles;  Used in ER/PR positive patients only  All age groups included now  Relatively safe  Easy to administer  Adequate prophylaxis against Carcinoma of opposite breast  Useful in Metastatic Carcinoma  Reduces recurrence – improves quality of life and longevity 114

108. Includes; Medical i. Oestrogen Receptor Antagonists – Tamoxifen 20 mg ii. Progesterone receptor Antagonist iii. Oral Aromatase Inhibitors – Letrozole 2.5 mg OD, Anastrozole, Exemestane; Aminoglutethimide [Medical Adrenalectomy] iv. Androgens – inj.Testosterone propionate 100mg IM three times a week, Fluoxymestrone 30 mg daily v. LHRH Agonists – Goserelin (Zoladex) [Medical Oophorectomy] vi. Progestogens – Medroxypregesterone acetate 400 mg Surgical i. Ovarian Ablation by a. Surgery (Bilateral Oophorectomy) b. Radiation ii. Adrenalectomy iii. Pituitary ablation 115

109. Tamoxifen  SERM (Selective Estrogen Receptor Modulator)  Blocks cytosolic ER in breast tissue  Dose: 10 mg BD or 20 mg OD for 5 days  T1/2: 7 days. Shows effects after 4 weeks  Cheap, easily available, effective  Indications:  Carcinoma Breast  Fibroadenosis  Male infertility  Desmoid tumours  Side-effects:  ‘Tamoxifen Flare’: Flushing, tachycardia, sweating, pruritis vulva, vaginal atrophy and dryness (pre-menopausal), vaginal discharge (post- menopausal), fluid retention, weight gain  Agonistic action: Endometrium (Ca), Bone (Osteoporosis, pathological #), Coagulation system (DVT, TIA, CVA, MI) 116

110. Letrozole  Non-steroidal competitive inhibitor of Aromatase Reduces Oestrogen levels by 98%  More expensive, more effective, fewer side-effects Indications: 1. Adjuvant Endocrine therapy in Post-menopausal women with hormone sensitive breast cancer 2. Metastatic disease 3. Recurrent disease  Dosage: 2.5 mg OD for 5 years or for 3 years after Tamoxifen  Side-effects: Vaginal atrophy, bleeding p.v, CVS problems and osteoporosis. 117

111. Novel drugs - Biologicals 1. TRANSTUZUMAB (Herceptin)  Monoclonal Ab. Blocks Her-2/Neu receptors (Tyrosine kinase receptor)  Useful only in Her-2/Neu +’ve cases Metastatic d/s  Intravenous infusion 4mg/kg loading, 2mg/kg maintenance dose for 1 year 2. BEVACIZUMAB Vascular Growth Factor receptor inhibitor 3. LAPITINAB Combined Growth Factor receptor inhibitor 118

112. IV. CHEMOTHERAPY Approach Types; A. Adjuvant Chemotherapy  Administration of Cytotoxics after surgery  Eliminate clinically undetectable distant spread B. Neoadjuvant Chemotherapy  Administration of Cytotoxics in large operable tumours before surgery  Reduce loco-regional tumour burden – downstage  Amenable to surgical resection after 3 doses C. Palliative Chemotherapy  Advanced Ca Breast  Metastatic Ca Breast 119

113.  Indications;  All node positive patients  Primary tumour >1cm in size  Advanced Ca Breast  Inflammatory Ca Breast  Metastatic Ca Breast  Drugs; 120 CMF Regime CAF Regime MMM Regime Cyclophosphamide Cyclophosphamide Methotrexate Methotrexate Adriamycin Mitomycin-C 5-Fluorouracil 5-Fluorouracil Mitozantrone

114. Chemotherapy Regimes  CAF and CMF – commonly used, monthly/3 weeks cycles for 6 months  Taxanes  Eg: PACLITAXEL and DOCETAXEL  G2/M phase arrestors  Use: Metastatic Ca Breast  1st line: CMF > CAF > MMM  2nd line: Taxanes  3rd line: Gemcitabine 121

115. SR_Ca_Breast_Rx 122

116. CARCINOMA BREAST in PREGNANCY - Management 1st Trimester 2nd Trimester 3rd Trimester MRM MRM MRM Axillary node +’ve: Termination of pregnancy + Chemotherapy Chemotherapy carefully After delivery – Chemotherapy with suppression of lactation 123 Note the following; Hormone treatment contra-indicated: Teratogenic Radiotherapy: No role MRI is the investigation of choice Can become pregnant 2 years after completion of therapy as recurrence rates are highest in 2 years

117. Follow-up  Clinical examination in detail at regular intervals  Yearly/2-yearly Mammography of the treated and contralateral breast is a must  Bone-scan, CT Chest/abdomen, tumour markers are done only if there is clinical suspicion. Not a regular routine follow-up at present 124

118. BREAST RECONSTRUCTION  Done in young patients with early stage of disease  Symmetry is the most important factor  Factors deciding reconstruction;  Amount of skin retained  Stage of Carcinoma  Earlier Radiotherapy  Type of flap used  Timing  Immediate Reconstruction: in Early stages with good response to neoadjuvants. Contraindicated in LABC  Delayed Reconstruction: 3-9 months after surgery. Done in LABC. Allows post-op RT without prosthesis exposure, avoids fibrosis and fat necrosis where TRAM flap in used 125

119. Methods of Reconstruction 1. Breast Implants – Silicone gel 2. Expandable Saline prosthesis 3. Flap with implant/expanders 4. External breast prosthesis 5. Flap reconstruction 1. Latissimus dorsi (LD) flap 2. Contralateral Tranversus Abdominis (TRAM) flap 3. Superior Gluteal flap 4. Ruben’s flap: soft tissue over Iliac crest 126

120. 127

121. SR_Ca_Breast_Rx 128

122.  Complications of Implants;  Pain, exposure of implant and rupture  Displacement, extrusion  Infection  Capsular contraction 129 LD Flap TRAM flap Myocutaneous flap Myocutaneous flap Subscapular artery Superior Epigastric artery Easy Ipsilateral or contralateral flap Can be placed over prosthesis Gives bulk. No need of prosthesis Reliable, well-vascularised Free TRAM flap into IMA Low complication rate Mesh placement in abdomen required Unsightly donor area on back Donor site morbidity & fat necrosis

123. Thank you 130

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