Locally advanced breast cancer

carcinoma brease , nccn guidelines

1. Management of L ocally A dvanced Breast C ancer

2. Anatomy

3. Arterial supply

4. Lymph Nodes

5. Ca Breast Clinical TNM stage

6. M stage

7. Staging

8. Locally advanced breast cancer LABC constitutes 10% to 20% of all breast cancers Stages IIIA, IIIB, IIIC P atients with large primary tumors (>5 cm ) T umors involving the chest wall S kin involvement, ulceration or satellite skin nodules B ulky or fixed axillary nodes C linically apparent internal mammary or supraclavicular nodal involvement Inflammatory breat carcinoma No clinical distant metastasis

9. Inflammatory carcinoma Rare, accounting for approx 1% to 5% of all breast tumors aggressive subtype of breast cancer Can occur with tumors of ductal or lobular histology Hallmark: Diffuse tumor involvement of the dermal lymphatic channels within the breast and overlying skin, often without an underlying tumor mass. Manifestation : Erythema, edema, and warmth of the breast as a result of lymphatic obstruction

10. peau d’orange : orange-peel appearance of the skin resulting from edema and dimpling at sites of hair follicles history should reveal a rapid onset of the disease, with progression over weeks to 3 months

11. Diagnosed clinically There may be no abnormality on mammography beyond skin thickening, and a palpable mass is not required for diagnosis Axillary nodal metastases are common Significant risk for distant metastases

12. Diagnosis Triple assessment History and physical examination Imaging Histopathology

13. History and Physical examination

14. Imaging Mammography r/o multifocal or multicentric disease Sensitivity – 90 % Specificity- 94%   Inflammatory breast carcinoma fine pleomorphic calcifications (circle) with associated diffuse skin thickening

15. Imaging USG breast : Dense breast Cyst from solid tumors Confirm physical and mammography findings Interventional procedures If both mammography and USG are negative then the negative predictive value is 99%

16.  MRI BREAST: More sensitive to reveal LABC extension and staging Sensitivity- 79.5% Specificity- 89.8% Used for surgical planning Response to neoadjuvant chemotherapy and offering BCS Detect tumor physiology by contrast enhancement Identify Tripple negative breast cancer based on enhancement and morphological pattern in MRI (high T2 signal intensity /homogeneous rim enhancement/Oval shape )

17. PET Scan: Sensitivity – 93%, specificity- 78 % Diagnose ,stage disease Identify tumor respone and recurrence Detect distance metastasis

18. Histopathology Core needle biopsy For differentiating ductal carcinoma in situ and invasive cancer Establising ER,PR and HER 2 status

19. Work up CBC Comprehensive metabolic panel, including liver function tests and alkaline phosphatase Chest diagnostic CT with contrast Abdominal ± pelvic diagnostic CT with contrast or MRI with contrast Bone scan or sodium fluoride PET/CT (category 2B) FDG PET/CT (optional )

20. Workup Determination of tumor ER/PR status and HER2 status Genetic counseling if patient is at risk for hereditary breast cancer Counseling for fertility concerns if premenopausal; pregnancy test in all women of childbearing potential Assess for distress

21. Algorithm for management contd. Operable disease

22. preoperative chemotherapy Standard treatment for inoperable breast cancer to render the disease resectable . To diminish the extent of the disease ( downstaging ) To assess for clinical and pathologic response of primary tumor and axillary nodes Multimodality treatment including surgery offers the highest likelihood for a successful outcome NAC for operable LABC : lower mastectomy rates Meig JSD et al.BJS;2007

23. Chemotherapy Anthracyclines (Doxorubicin aka Adriamycin, Epirubicin ) - topoisomerase II inhibitor and antimetabolite - ADR- Cardiomyopathy, leukemia Taxanes (Paclitaxel, Docitaxel ) - microtubule inhibitor - peripheral neuropathy Transtuzumab : trigger HER 2 internalization and degradation through promoting activity of tyrosine kinase – ubiquitinin ligase c- Cbl

24. Factors a/w good response : Lower hormone receptor levels HER 2 positive Higher tumor grade IHC: Ki-67

25. Role of neoadjuvant endocrine therapy(NET) Advantage : Examine mechanisms of resistence Optimize and compare therapies Indicated in ER positive /HER2 negative Intolerant to Neoadjuvant chemotherapy Elderly females who cannot tolerate surgery Mainly for post menopausal female Useful for patients with PEPI=0 (ALTERNATE TRIAL ) NET has similar outcome with a better QOL Madigan et al.breast cancer research;2020

26. NET agents selective ER modulators: tamoxifen Selective estrogen degraders : fulvestrant Aromatase inhibitors : letrozole , anastrozole Duration : 3-4 months IMPACT Trial: anastrazole non inferior to tamoxifen PO24 trial : letrozole led to higher rate for BCS and objective response rate

27. Role of neoadjuvant radiotherapy Little studied Not considered in carcinoma breast

28. Measurement of response Image response : MRI Breast RECIST : Complete response: primary tumor disappearance Partial response : >30% or more decrease inlongest diameter of primary tumor Progressive disease :20% or greater increase in inlongest diameter of primary tumor Stable disease : no significant shrinkage

29. Preoperative endocrine prognostic index(PEPI ) Includes : tumor size nodal status KI67 levels ER status To identify recurrence free survival rate 0=10% relapse risk 1-3=23% >3=48%

30. Indications for sentinel lymph node biopsy Planned at the time of definitive primary surgery in patient with negative axillary work up on the original , prechemotherapy assessment Tan VK et al ;J surg Oncol.2011

31. Surgical options Breast conservation Surgery vs mastectomy Mastectomy--- standard of care . Indications for BCS noninflammatory   labc small N2 or N3 tumours with nodal response large tumours (T3N0 or T3N1) with good response after neoadjuvant chemotherapy

32. Algorithm for management contd.

33. Tripple negative breast cancer Frequnet in young and premenopausal women Donot benefit from hormonal and transtuzumab based therapies Biologically aggressive Antracycline -cyclophosphamide based chemotherapy Cisplatin + epirubicin+paclitaxel cyclophosphomide+methotrexate+5-fluorourcil

34. SURVEILLANCE/FOLLOW-UP Exam : History and physical exam 1–4 times per year as clinically appropriate for 5 y, then annually Genetic screening : Periodic screening for changes in family history and genetic testing indications and referral to genetic counseling as indicated, Post surgical management: Educate, monitor, and refer for lymphedema management, Imaging: Mammography every 12 months Routine imaging of reconstructed breast is not indicated

35. Screening for metastases : In the absence of clinical signs and symptoms suggestive of recurrent disease there is no indication for laboratory or imaging studies for metastases screening Lifestyle : active lifestyle, healthy diet, limited alcohol intake, and achieving and maintaining an ideal body weight (20–25 BMI)

36. Endocrine therapy : Assess and encourage adherence to adjuvant endocrine therapy Women on tamoxifen : annual gynecologic assessment every 12 months if uterus present Women on an aromatase inhibitor or who experience ovarian failure secondary to treatment : monitoring of bone health with a bone mineral density determination

37. Communication: Coordination of care between the primary care provider and specialists personalized survivorship treatment plan including personalized treatment summary of possible long-term toxicity and clear follow-up recommendations Engagement : Patients frequently require follow-up encouragement in order to improve adherence to ongoing screening and medication adherence

38. Increased risk in patients with N2/N3 disease or >2 cm residual tumor Work up : History and physical exam Discuss goals of therapy, adopt shared decision-making, and document course of care CBC Comprehensive metabolic panel, including liver function tests and alkaline phosphatase Recurrence

39. Chest diagnostic CT with contrast Abdominal ± pelvic diagnostic CT with contrast or MRI with contrast Brain MRI with contrast if suspicious CNS symptoms Spine MRI with contrast if back pain or symptoms of cord compression Bone scan or sodium fluoride PET/CT (category 2B)

40. FDG PET/CT(optional ) X-rays of symptomatic bones and long and weight-bearing bones abnormal on bone scan First recurrence of disease should be biopsied Determination of tumor ER/PR and HER2 status on metastatic site For biomarker testing to identify candidates for additional targeted therapies, Genetic counseling if patient is at risk for hereditary breast cancer

41. References Sabiston’s textbook of Surgery NCCN guidelines 2020 Fischer Mastery of Surgery M. Brackstone et al.Curr Oncol . Locoregional therapy of locally advanced breast cancer: a clinical practice guideline 2015 Mar; 22( Suppl 1): S54–S66.