Management of axilla in carcinoma breast

Management of axilla in carcinoma breast

1. Management of Axilla in Ca Breast Presenter : Dr Sagar N Raut Moderator : Dr Laxman Pandey 29-07-2019

2. Topics covered Introduction Anatomy of axilla Lymphatic drainage of breast Staging Treatment Node negative Node positive

3. Introduction Nodal metastasis - key prognostic predictor. Determines the need for systemic therapy , the extent of surgery , reconstruction options , and the need for radiation after mastectomy . Historically - Axillary node dissection ( ALND ) to stage the axilla .

4. ANATOMY Mammary gland lymphatics begin in the interlobular or prelobular spaces, follow the ducts, and end in the subareolar network of lymphatics of the skin . Predominant lymphatic drainage - axillary lymph nodes

5. 3 Levels level III without level I or II - unusual . Level III continues to supraclavicular lymph nodes . Axilla is the most common site Regardless of location in the breast.

6. STAGING OF THE AXILLARY NODAL REGIONS Physical examination of regional nodal basins. Determine the size and if matted or not . Unfortunately , physical examination is impacted by body habitus , making it highly unreliable with a false-negative rate ( FNR ) as high as 45 % (1) 1. Sacre R. Clinical evaluation of axillar lymph nodes compared to surgical and pathological findings. Eur J Surg Oncol 1986;12:169–73.

7. Staging (Cont..) U ltrasound ( US ) - preferred nodal assessment before therapy. Benefit - needle biopsy for pathologic confirmation. Axillary US with fine-needle aspiration (FNA) of abnormal nodes have (1) Sensitivity - 86.4% ( 93 % if metastatic deposits > 5 mm vs 44% for < 5 mm ), Specificity - 100% , and Negative predictive value - 67 % . Place clips to mark nodes with biopsy - confirmed disease. 1 .Krishnamurthy S, Sneige N, Bedi D, et al. Role of ultrasound-guided fine-needle aspiration of indeterminate and suspicious axillary lymph nodes in the initial staging of breast carcinoma. Cancer 2002;95:982–8.

8. Staging

9. Surgical Axillary Staging Sentinel lymph node mapping and excision Axillary lymph node dissection

10. In brief about sentinel biopsy procedure Sentinel lymph node - First node to receive lymphatic drainage from a specific area of breast Most likely to contain metastasis if tumor has metastasized Accuracy increases when both blue dye and radioactive colloid (Tc 99m sulphur colloid) are used together.

11. Rationale is to identify subset of patients with negative sentinel lymph nodes These patients can avoid subsequent axillary dissection & morbidity With SLND for axillary staging - accurate staging while minimizing morbidity. First introduced for melanoma in early 1990s, & also validated in breast cancer

12. CLINICALLY NEGATIVE LYMPH NODE

13. CLINICALLY NEGATIVE LYMPH NODE ALND - risks of lymphedema, chronic pain, and sensory deficits. SLND - currently the standard approach for axillary staging in clinically (-ve) axilla . If SLNs – (-ve) for metastasis , then a completion ALND is not required.

14. Important Trials of SLNB

15. Demonstrated decreased incidence of lymphedema in the SLND arm (RR 0.37 ; 95% CI , 0.23–0.6 ). Also SLND group had lower drain usage , hospital stay , and a shorter time to return to normal activities with improved quality-of-life scores

16. 516 patients with T1 tumors randomized to RESULTS — Overall accuracy of the sentinel node status was 96.9% , the sensitivity 91.2% , and the specificity 100% Less pain and better arm mobility in SLNB group 1. Sentinel LN biopsy (If +ve---Axillary dissection done ) 2. SLNB f/b Axillary dissection

17. Sample size: 5611

18. No differences in disease free ( 82.4% vs 81.5 % ) or overall survival ( 91.8% vs 90.3 % ) rates at 8 years.

19. Positive Sentinel node biopsy – Sentinel node biopsy alone or axillary lymph node dissection? Eligibility: T1, T2 tumour 1 or 2 positive sentinel LN Breast conserving surgery Whole breast RT planned by tangential fields (No 3 rd axillary field) No pre-op chemotherapy

20. Median follow-up time - 6.3 years

21. This land mark trial findings confirmed the safety of omitting ALND in T1 or T2 breast tumours with <3 LN. 10-year of follow up has confirmed the absence of a difference in outcomes between the two groups

22. SLNB controversial for multi-centric disease, Post NACT, prior RT or SX

23. Designed for HIGHER risk sentinel node +ve patients who DO NOT fit into ACOSOG Z0011 criteria ( eg : 3 sentinel node+ve ) First trial to COMPARE prospectively axillary LN dissection Vs axillary RT in such patients.

24. RESULT- Lymphoedema noted to be significantly higher after axillary LN dissection than after axillary RT

25. Management of Positive Sentinel Lymph Nodes (cont..) - Micrometastatic With the incorporation of SLND, pathologists could focus on a smaller number of nodes and began to perform more detailed evaluation. This has led to a growing proportion of patients diagnosed with micrometastatic (defined as > 0.2mm but <2 mm ) or very low volume nodal disease . ( 1) 1. Giuliano A, Dale P, Turner R, et al. Improved axillary staging of breast cancer with sentinel lymphadenectomy. Ann Surg 1995;222:394–9.

26. Two other randomized trials have evaluated patients with micro metastasis (>0.2 mm but ≤ 2 mm) , the IBCSG 23-01 trial (primary tumour <5cm ) and AATRM trial (primary tumour <3.5cm ). Both showed no statistical significance in disease free survival . Findings of these trials were incorporated into NCCN Clinical Practice Guidelines in Oncology and ASCO guidelines.

27. Management of Positive Sentinel Lymph Nodes (cont..) - Isolated tumor cells TNM staging system pN0( i +) Isolated tumour cells (ITCs), Clusters of metastatic deposits < 0.2 mm , single tumour cells or clusters of <200 cells in a single cross-section . With the spread of SLND, the use of immunohistochemistry (IHC ) became more popular . ITCs diagnosed more frequently

28. 5210 patients 5119 SLN specimens (98.3%), 3904 (76.3%) were tumor-negative by hematoxylin-eosin staining 3326 SLN specimens examined by immunohistochemistry, 349 (10.5%) were positive for tumor No difference in 5-year OS between IHC -ve and IHC +ve (95.7% vs 95.1%; P = .64).

29. Cont.. Similarly, a subgroup analysis of NSABP B-32 showed, 15.9% of patients with H&E-negative SLNs were +ve by IHC ( 11.1% ITCs, 4.4% micrometastases , and 0.4% macrometastases ). 5-year OS statistically significant but with very small difference ( 94.6% in IHC-positive patients vs 95.8% in IHC-negative patients; P = .03 ).

30. Are ITCs clinically relevant?? Yes Where? Lobular tumours (1) Reason? Lobular cancer cells have noncohesive growth patterns (2) Nodal metastases may present as widely dispersed ITCs. Thus some still perform IHC of SNLs in patients with lobular cancers and consider ALND when isolated tumour cells are identified Mittendorf EA, Sahin AA, Tucker SL, Meric-Bernstam F, Yi M, Nayeemuddin KM, Babiera GV, Ross MI, Feig BW, Kuerer HM , Hunt KK. Lymphovascular Invasion and Lobular Histology are Associated with Increased Incidence of Isolated Tumor Cells in Sentinel Lymph Nodes from Early-Stage Breast Cancer Patients . Ann Surg Oncol . 2008;15(12):3369-77 . Cserni G, Bianchi S, Vezzosi V, et al. The value of cytokeratin immunohistochemistry in the evaluation of axillary sentinel lymph nodes in patients with lobular breast carcinoma. J Clin Pathol 006;59:518–22 .

31. Elderly Patients In 2016, the Society of Surgical Oncology joined the American Board of Internal Medicine Foundation in their Choosing Wisely campaign. One of the recommendations included omitting the routine use of SLND in women > 70 years old with clinically node-negative , hormone receptor–positive breast cancer.

32. 10-year follow-up, Only 3% died from breast cancer, Adjuvant radiation therapy after breast-conserving surgery did not alter Overall survival, and Local recurrence and Axillary recurrence rates were low.

33. Importantly, this trial was conducted before the widespread acceptance of SLND, so 60% of the participants had no surgical staging of the axilla. Thus these results could be based on classifying patients as node negative on clinical evaluation alone . As per NCCN : SLND optional in elderly patients

34. SLNB post neoadjuvant chemotherapy The timing of SLNB is controversial. Data from M.D. Anderson Cancer Centre have shown that comparable false negative rates ( 5.9% vs. 4.1% in neoadjuvant and in surgery first group respectively, p=0.39) with no significant differences in overall or disease free survival rates . Significantly lower rates of positive SLNs in T1 to T3 tumour categories T1 tumours : 12.7% vs. 19% , p=0.02 ; T2 tumours : 20.5% vs. 36.5% , p<0.0001; and T3 tumours : 30.4% vs. 51.4 %, p=0.04.

35. Dual tracer method with removal of ≥2 sentinel nodes are recommended to reduce the false negative rates associated with SNB after neoadjuvant therapy .

36. Management of the clinically positive axilla

37. ALND is still considered as the routine standard for patients with clinical, radiologically or pathologically proven positive axillae. Also when SLNB fails or when it is contraindicated (inflammatory breast cancer) .

38. ALND (cont..) Standard ALND is an anatomic resection of the level I and II axillary regions ( At least 10 nodes ) with care to preserve the axillary vein, thoracodorsal neurovascular bundle, and the long thoracic nerve . level III NOT REMOVED ROUTINELY (unless clinical evidence involvement) ( 1.4% if level I & II –ve).

39. Axillary node dissection (Cont..) Rationale - -- Allows proper staging Yields diagnostic information Guides subsequent treatment Removes tumor for potential therapeutic gain Diminishing risk of axillary recurrence Upto 20-40% of T1 &T2 cN0 may have pathologically involved lymph nodes. If nodal dissection is not performed in such tumors, the axillary failure rate is approx 20 %

40. Disadvantage - ---Higher incidence of breast and arm edema Axillary dissection can be spared in- -- Older patients ( 70-80 yrs ) with T1N0 breast cancers Certain tumor types ( Tubular/Medullary/Mucinous )

41. Complications of  ALND

42. Neurovascular Injury The long thoracic nerve : < 1% of cases. Winged scapula The thoracodorsal nerve : no significant neurological deficit The intercostal brachial nerve : paresthesia at the medial half of the upper arm. Injury to the medial pectoral nerve - atrophy of the major pectoral muscle.

43. Seroma Forms in nearly all cases to some extent However , prolonged seroma - infection and delays adjuvant treatment. A low-pressure suction drain . Because prolonged seroma - drain is a source of infection - percutaneous aspiration. One effective method is delaying exercise and complete shoulder movements until after the fifth day following the operation.

44. Lymphedema Lymphedema of up to 1–2 cm is considered mild and is observed in 20–30% of patients with level 1–2 ALND.  Larger swelling is considered a serious lymphedema and is observed in less than 5% of patients. The risk of lymphedema in patients with level 3 ALND is 30%, and therefore level 3 ALND is not performed without a valid reason. Mild lymphedema can be observed in 5% of patients following SLNB .

45. Prevention - ARM The detection and preservation of lymphatics of the arm in the axilla using the injection of blue dye into the upper arm is called reverse axillary mapping. Technique : injecting 2.5 to 5 ml of blue dye subcutaneously in the upper inner arm along the medial intramuscular groove of the ipsilateral arm.

46. Neo-adjuvant Chemotherapy Pts with clinically +ve node often receive NAC - can eradicate nodal disease in 40% of patients. (1) Nodal conversion rates depending on the receptor status of the tumour (1) 21.1% for ER/PR positive, HER-2 negative tumours; 49.4% for triple negative tumours and 64.7% for HER-2 positive tumours. Dual tracer technique and removal of ≥3 sentinel lymph nodes have shown to reduce FNR. Boughey J, McCall L, Ballman K, et al. Tumor biology correlates with rates of breast-conserving surgery and pathologic complete response after neoadjuvant chemotherapy for breast cancer: findings from the ACOSOG Z1071 (alliance ) prospective multicenter clinical trial. Ann Surg 2014;260:608–14 . Boughey JC, Suman VJ, Mittendorf EA, Ahrendt GM, Wilke LG, Taback B, Leitch AM, Kuerer HM, Bowling M, Flippo -Morton TS . Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance ) clinical trial. JAMA. 2013;310(14): 1455-61

47. With increasingly high nodal conversion rates, clinicians have questioned the use of extensive axillary surgery in patients who have no residual nodal disease. P=0.05

48. US alone was not predictive of nodal response . In 430 patients who had normalized nodes on US after NAC, 243 ( 56.5 % ) had residual pathologic disease. Alternatively , 28.2% (51/181) of patients with nodes that looked suspicious on US after NAC had a nodal pathologic complete response .

49. ACOSOG Z1071 (Cont..) Usefulness of placing a nodal clips In 75.9% patients with >2 SLNs retrieved, the clip was found to be inside the retrieved SLN with a FNR of 6.8 % ( 95% CI=1.9%–16.5 %). Higher FNRs if clip was not used or when the clip could not be retrieved during surgery ( 13.4% and 14.3% , respectively) Targeted axillary dissection removes both the sentinel nodes and the clipped node, help minimize morbidity of ALND while maintaining an acceptability low FNR.

50. Radiotherapy in Axilla

51. Indications of RT to axilla

52. Reduction of locoregional recurrence with addition of RNI to WBRT or chest wall have been demonstrated in several trials. (1-6) But improvement in OS and breast cancer–specific survival rates was not noted uniformly across trials. Early Breast Cancer Trialists ’ Collaborative Group (EBCTCG). Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet . 2014;383:2127-35. Overgaard M, Hansen PS, Overgaard J, et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b trial. N Engl J Med. 1997;337:949-55. Overgaard M, Jensen M, Overgaard J, et al. Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen : Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet. 1999;353:1641-8. Poortmans PM, Collette S, Kirkove C, et al. Internal mammary and medial supraclavicular irradiation in breast cancer. N Engl J Med. 2015;373:317-27. Ragaz J, Jackson SM, Le N, et al. Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. NEngl J Med. 1997;337:956-62. Whelan TJ, Olivotto IA, Parulekar WR, et al. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015;373:307-16.

53. High axillary nodal disease burden (≥ N2 disease) The absolute benefit (in locoregional recurrence & OS ) from RT in N+ dependent on the number of involved axillary nodes.[27,28] Meta-analyses of intergroup trials and EBCTCG review shown that presence of ≥4 + ve axillary LN (N2 and N3) A/W significantly risk of locoregional recurrence. Thus , there is relatively little controversy over the management of N2 or N3 disease

54. The 5-year survival rates can range from less than 65% for patients with >4 involved axillary lymph nodes to >95 % for breast cancer patients with pN0 . (1) 1. Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer. 1989;63:181-7

55. Q- What about 1-3 positive lymph nodes ?? 2 recent trials have clarified the situation--- NCIC—CTG MA.20 EORTC 22922/10925

56. ELIGIBILITY CRITERIA — Invasive female breast cancer BCS with Level 1/2 axillary dissection or SLNB Systemic chemotherapy / hormonal therapy / both MODERATE TO HIGH RISK of regional recurrence--- Involved axillary lymph nodes+ IF NO lymph nodes+ then either Grade 3 / LVE ER NEGATIVE ˂10 LN REMOVED

57. Study schema Breast conserving surgery plus axillary dissection and systemic therapy Stratify--- Number of positive nodes (0, 1-3 , >3) Number of nodes removed (<10, >10) Type of chemotherapy (i.e., anthracycline , other, none) Hormonal therapy (yes, no) RANDOMIZED Breast ALONE radiation Breast AND nodal radiation Nodal RT volume- -- Ipsilateral Internal mammary lymph nodes in upper 3 IC spaces Supraclavicular & axillary lymph nodes Dose--- 50Gy/25# to breast and nodal sites with 10-16Gy boost

58. RESULT No increase in rate of brachial neuropathy/cardiac disease in RNI group CONCLUSION– Addition of regional nodal RT to whole breast RT (even in 1-3+LN ) did NOT OS , but significantly increased DFS by 24 % , in both loco-regional & distant recurrences. WBI WBI + RNI OVERALL SURVIVAL (10 YEARS) 81.8% 82.8% (p- 0.38 ) DISEASE FREE SURVIVAL (10 YEARS) 77% 82% (p- 0.01) LR-DFS 92.2% 95.2% (p-0.009) DISTANT- DFS 82.4% 86.3% (P- 0.03 )

59. Stage 1/2/3 ca breast Centrally/medially located with ± axillary nodes Externally located with + axillary nodes R andomised Whole-breast or thoracic-wall irradiation in addition to regional nodal irradiation ( nodal-irradiation group) W hole-breast or thoracic-wall irradiation alone (control group)

60. Total 4004 patients

61. Post Neoadjuvant chemotherapy

62. Completion ALND for mastectomy patients with a positive SLNB remains the standard of care

63. Axillary Recurrence

64. ONGOING CLINICAL TRIALS National Surgical Adjuvant Breast and Bowel Project B-51/Radiation Therapy Oncology Group 1304 Trial A randomized phase III study (ClinicalTrials.gov identifier: NCT01872975 ) Began enrollment in 2013. The main goal of the study T o evaluate the benefit of nodal radiation in clinically node positive patients with a complete nodal response after NAC.

65. Alliance A11202 Trial (ClinicalTrials.gov identifier: NCT01901094) Looking for an option for patients with residual positive SLNs after NAC. Patients are randomized to ALND versus no further axillary surgery and all patients receive regional nodal irradiation. The primary endpoint of the study is recurrence. The secondary outcomes include survival , regional recurrence, lymphedema development, adequacy of radiation fields, and residual cancer burden.

66. Thank You

67. The axilla is bordered by the latissimus dorsi posteriorly , the axillary vein superiorly, the chest wall medially, the pectoralis muscles anteriorly and extends laterally to where the vein crosses between the lateral edge of the pectoralis major and latissimus dorsi muscles. Level I nodes are located inferior and lateral to the pectoralis minor muscle , level II nodes posterior to the pectoralis minor and below the axillary vein, and level III nodes are medial to the pectoralis minor and below the clavicle. Lymphatic drainage generally follows an orderly sequential pattern from level I to level II nodes and rarely to level III.

68. Axillary lymph node dissection (ALND) has been an integral component of the staging, prognosis, and treatment of invasive breast cancer and is discussed in Chapter 38. Surgical management of the axilla, however, has undergone a paradigm change since the concept of lymphatic mapping of the breast was introduced at the John Wayne Cancer Institute ( JWCI) in 1991, and sentinel lymph node biopsy (SNB) has replaced ALND for axillary staging in clinically node-negative early breast cancer

69. In the early 1970s, Kett et al. (1) reported that the first regional lymph node, the “ Sorgius node,” could be identified in breast cancer using direct mammalymphography . This was a cumbersome technique that required a formal ALND to isolate the suspected lymph nodes, radiographic evaluation of the resected nodes to identify the suspicious ones , and determination of concordance through histopathologic confirmation .

70. Ramon Cabanas (2) coined the term sentinel node as a specific lymph node group in penile carcinoma, located in a constant anatomic location in the pelvis. The sentinel node ( SN) concept evolved from this observation of specific anatomic nodal drainage and postulates that a primary tumor is drained by an afferent lymphatic channel that courses to the first, “sentinel,” lymph node in that specific regional lymphatic basin (3). If the tumor has metastasized, it will do so to this node. The tumor status of the SN reflects the tumor status of the nodal basin. Morton et al. (4) tested the hypothesis that the SN in a given regional basin can be identified by an indicator dye in a feline model and then validated it in the clinical setting in a group of patients with melanoma.

71. Identification of a Sentinel Node in Breast Cancer The feasibility of identifying an SN intraoperatively in breast cancer was first investigated at the JWCI by Giuliano et al . ( 5). In October 1991, the authors’ group began to investigate the feasibility of lymphatic mapping and sentinel lymphadenectomy with isosulfan blue vital dye in breast cancer as a more accurate and less morbid approach to stage breast cancer (Fig. 37-1 ). This prospective study demonstrated that SNB of the axilla is technically feasible, safe, and without added complications. With a defined technique and experience , a 100% accuracy to predict the status of the axilla was subsequently achieved (5,6).

72. In addition to vital dye-directed lymphatic mapping, three other technical approaches for SN identification in breast cancer with accuracy rates comparable to the blue dye have evolved: radio-guided surgery , radio-guided surgery with preoperative lymphoscintigraphy , and the combination of vital dye and isotope techniques. The most commonly used agents are isosulfan blue dye and filtered technetium sulfur colloid. An increased SN identification rate with the use of the combination of blue dye and radioisotope is well documented. However , there has been only one prospective randomized trial comparing blue dye alone to the combined use of isotope and blue dye, and in this study Morrow et al. showed no difference in SN identification between the two groups (7).

73. SNB is a staging procedure that removes one or more lymph nodes from the axillary basin. The SN is found in level I in 83% of cases, level II in 15.6%, in level III in 0.5%, internal mammary in 0.5%, supraclavicular in 0.1%, and elsewhere in 0.3% (10).

74. Axillary Sentinel Lymph Node Biopsy Technique If using radioisotope, intradermal, subdermal, or peritumoral injection of a single dose of 0.3 to 1.0 mCi of technetium-99m sulfur colloid is performed 3 to 24 hours prior to incision. Lymphoscintigraphy may be performed after injection to document migration of the radioisotope. Intraoperative subareolar or dermal injection of radioisotope approximately 40 minutes prior to incision has been reported to localize the SN in 98.6% of the cases (419/425) of sub areolar radiotracer alone , 94.8% (326/344) in dual injection, and 100 % (6/6) in dermal injection (69). When radioisotope is used , the incision is made directly over the location of a focal site of increased activity and dissection proceeds until the SN is identified by quantitative counts and resected.

75. A radioactive node has been defined as a node with a cumulative 10-second count of greater than 25, the hottest node by absolute counts, a 10 to 1 ratio of SN to background , or a fourfold reduction in counts after the SN is removed ( 70). Verification is done by ex vivo SN counts compared to residual in vivo background counts. Additional radioactive SNs are removed until the background is less than one-tenth the value of the hottest node. Lymph nodes with the highest radioactive uptake usually contain the greatest tumor burden , but on occasion tumor replaced nodes may have lymphatic obstruction , and if only the hottest node is removed , a positive SN with lower counts may be missed in 23% of cases (71).

76. If blue dye is employed, 3 to 5 mL is injected approximately 5 to 10 minutes prior to incision. The addition of a post-injection massage has been shown to improve the uptake of blue dye by SNs, further increasing the sensitivity of this procedure (72). After a 2 to 3 cm transverse incision is made in the axillary fossa, a careful search for all blue nodes or lymphatics should be carried out. Palpation of the axillary space for any suspicious nodes will avoid missing a tumor-laden node that has occluded lymphatics and may not be blue or radioactive. All suspicious palpable nodes must be removed at the time of SNB, regardless of technique—isotope or dye.

77. RESULT - Median follow-up time - 6.3 years, The reasons for this result could be— Favourable subset of patients chosen in this trial with low likelihood of high residual axillary disease INCLUSION CRITERIA AVERAGE PATIENT IN TRIAL ALND SLND local recurrence 3.6% 1.8% P = 0.11 regional recurrence 0.5% 0.9% P = 0.45 5-year overall survival 91.9% 92.5% P = 0.24

78. 2-- Use of systemic therapy 3-- Incidental radiation to the residual nodes in level I or II from the tangential breast irradiation These results are potentially PRACTICE CHANGING However , they DO NOT apply if— Patient is undergoing mastectomy Patient will not receive tangential whole breast RT Involvement of ˃ 2 sentinel nodes Patient has received neo-adjuvant therapy .

79. Indications for completion ALND in pts with + ve SLNB Absolute T3-T4 disease ≥3 positive SLNs 1 or 2 SLNs not receiving WBRT Relative Extranodal extension T1-T2/N1mi-N1 with young age, negative hormone receptor status, high histologic grade, lymphovascular space invasion, and size of nodal metastatic deposit

80. Treatment Regular trunk cleaning and massage, which is called manual lymphatic drainage, are applied to patients by trained physiotherapists, and bandaging is applied. If no response is obtained using these procedures and if fibrosis has begun in the arm, laser therapy (low-level laser therapy) can be attempted. Laser therapy resolves fibrotic scar tissue by acting on fibroblasts and stimulates lymphatic drainage. have a lymphedema-reducing effect in 52% of cases.

81. There is still a controversy surrounding the management of pre-neoadjuvant node-positive patients who become node negative after neoadjuvant chemotherapy. At present, here is insufficient good quality data evaluating the oncological outcomes of excluding ALND in this group of patients. However, some are already practising SLNB instead of primary ALND for these patients