Clinical Evaluation of breast carcinomaa

Clinical approach on how to evaluate a case of breast lump

1. By S2 unit - under guidance of Professor J. Kishore and faculty members Breast carcinoma

2. Risk factors Increasing age Early menarche ( 10-12 yrs ) Late menopause Family history - one first degree relative with breast cancer increases cancer risk by 300% in suspect Hormonal replacement therapy (E+P ) Maternal age at first live birth ( if at or less than 20 yrs - protective ) Breast feeding _ at least for 1 year is protective Genetics - BRCA1 and BRCA 2

3. Why are risk factors important from a surgeon’s perspective ? They help us in calculating risk assessment scores , which in turn curate screening protocol for breast cancer . Most commonly used are - GAIL model , Tyrer Cuzick Model Gail model includes - age of person , age at menarche , age at first live birth , previous breast biopsies , family history ( first degree relatives )

4. Why are mutations important from surgeon’s perspective ? BRCA 1 and BRCA 2 BRCA mutation predispose a patient to HBOC ( Hereditary breast and ovarian cancer ) syndrome — — so the first degree relatives need to be screened — lifestyle changes need to be advised - weight reduction , regular exercise , quit smoking Risk reduction techniques can be used in these patients- they are ॰ Bilateral prophylactic mastectomy ॰ Risk reducing salpingo - oophorectomy

5. A 45yr old female with complaints of lump in right breast since 6 months rapidly increased in size to attain present size of 4 X 4 cm..………… What is the radiological investigation of choice ?

6. Mammogram WHY ?? As the age increases breast tissue is replaced by fat and increasing fat component in breast gives a good contrast against the tumor It also helps us assess the percentage of glandular component ( more glandular component - better outcomes in Onco plastic breast surgery )

7. Mammography findings Benign Malignant Well differentiated Irregular speculated lesion Halo surrounding lesion Architectural distortion Macro calcification Microcalcifications
(Cluster > linear > segmental > diffuse )

8. 3D Mammography A/k/a Breast tomosynthesis It is a latest form of mammography More sensitive Gives better results in a dense breast Less recall rates

9. BIRADS Needs additional imaging Recall additional imaging 1 Negative Routine screening 2 Benign Routine screening 3 Probably benign Short interval follow up ( every 6 months ) over 2 yrs 4 Suspicious Tissue diagnosis 5 Highly s/o malignancy Tissue malignancy 6 Biopsy proven malignancy Surgical excision

10. Other radiological investigations USG -done in younger females with dense breasts -in a pregnant lady with a lump MRI - IOC in pts with breast implants - Differentiates between multifocal and muticentric tumors -IOC to identify local/scar recurrence after surgery -patient with a suspected ducal lesion but inconclusive USG -assessing of treatment response after NACT -Screening modality for high risk patients

11. Pt 45yrs old BIRADS -4c with a palpable breast lump 4cm in UOQ ……………next investigation

12. Tissue diagnosis FNAC , TRUCUT , EXCISIONAL BIOPSY IOC - TRUECUT BX - -differentiates between in-situ and invasive -ER,PR,HER 2 NEU status can be obtained Gold standard - excisional biopsy

13. Pt 45yrs old came for annual screening mammogram. It shows BIRADS -4c in Rt side with a clinically no palpable breast lump ……………next step

14. Techniques for biopsy of a non palpable breast lump Ultrasonography- intra operative USG can be used to localise and remove Wire - placed through an introducer needle under image guidance , has a hook that engages with breast parenchyma at or near the abnormality Radioactive seed localisation - Iodine 125 radioactive seed of size 4.5mm are advanced with a needle under USG or mammogram guidance to the lesion of interest , in OR gamma probe is used to guide

15. Molecular classification based on ER /PR /HER2NEU ER PR HER2/NEU Ki67 Luminal A
mc subtype
Best prognosis + + - Low Luminal B (majority) + + + Low/high Luminal B ( minority) + + — High Basal type :
TNBC
Worst prognosis
High incidence of visceral metastasis — — — High Claudin low
Cytokeratin5/6 - — — — High Her2/NEU enriched — — + Low/high

16. Staging of breast cancer TNM T1- tumor <2cms T2 - tumor 2-5 cms T3 - >5 cm T4a-extension to the chest wall T4b-skin involvement ( ulceration , satellite nodules , edema ) T4c-both 4a and 4b T4d- inflammatory carcinoma

17. N staging N1-mobile axillary lymph nodes N2a - fixed or matted axillary lymph nodes N2b- internal mammary lymph nodes + absence of axillary lymph nodes N3a- ipsilateral infra clavicular lymph nodes N3b-internal mammary + axillary N3c- supraclavicular lymph nodes

18. M staging M 0 - no distant metastasis M 1 - distant metastasis + Distant metastasis - mc site - bone mc bone - vertebral column mc vertebrae- lumbar > thoracic osteolytic >osteoblastic

19. Staging Early breast cancer - T1 N0 , T1 N1 , T2 N0 , T2 N1 Locally advanced breast carcinoma - T3 N0 ,T3 N1 M0 , Any T4, Any N2 , Any N3 Metastatic breast cancer T any , N any , M1

20. Treatment options for breast cancer Surgery Chemotherapy Harmonal therapy Radiotherapy

21. A case of 53yr old female with right breast lump of size 4cm ,with no skin involvement , with no palpable LNs Mammogram-BIRADS-4b CNB- ER,PR+ ,her2neu -

22. Stage - T2 ,N0,M0 Early breast cancer BCS MASTECTOMY IF BCS IS C/I N0 - SENTINEL LN BIOPSY CHEMOTHERAPY - IF GENOMIC ASSAY SCORE >25 Radiotherapy Harmonal therapy with aromatase inhibitors

23. Breast Conservative surgery Can be done in cases of early breast cancer Done when tumor to breast ratio is less than 20% Margin ? A case of BCS is always followed by radiotherapy

24. Contra indications for BCS Contraindications for radiotherapy -pregnancy -active SLE -Rhematoid arthritis -scleroderma -prior radiotherapy exposure to chest wall Multicentric and multi focal tumors Lobular cancer- as they are multicentric and bilateral BRCA 1 and BRCA 2

25. A case of 53yr old female with right breast lump of size 4cm ,with no skin involvement , with no palpable LNs Mammogram-BIRADS-4b CNB- ER,PR+ ,her2neu - is axillary clearance warranted ??

26. Sentinel lymph node biopsy Sentinel/gaurding lymph node is the first draining lymph node from cancer Also used in - - vulvar carcinoma - malignant melanoma - penile cancer - head and neck cancer Techniques - -blue dye technique -radio nucleotide technique -sentimag technique -fluorescent light

27. Blue dye technique Methylene blue MC used 1.5-2 cc injected ( 15-20 mins prior ) Periareolar > peritumoral In s/c plane > intradermal inj ( increased risk of skin necrosis ) Axilla is opened and LN identified and sent for frozen section If frozen section is + —> axillary LN clearance done Complications - skin tattooing (mc ) , anaphylaxis , skin necrosis , bluish discolouration of urine

28. Radio-nucleotide method Tc-99 tagged sulphur colloid is injected at NAC and baseline value noted Gamma camera is used to detect radio-activity It makes a noise when it reaches the lymphnode Any LN having 10% of baseline value is a + LN BEST technique - combination of blue dye + radionucleotide

29. A case of 53yr old female with right breast lump of size 5cm ,with no skin involvement , with 2 palpable axillary Level 1 LNs Mammogram-BIRADS-4b CNB- ER,PR+ ,her2neu - next step ….

30. Chemotherapy Indications - Lymph nodes + Locally advanced breast cancer ER,PR -ve Hr2neu +

31. Drugs Anthracyclines - doxorubicin , epirubicin , s/e-cardiotoxicity Taxanes - paclitaxel , docetaxel , s/e - peripheral neuropathy Cyclophosphamide Methotrexate F 5-fluorouracil 4AC F/B 4T OR 4AC F/B 4T Earlier regimens used were - CMF , CAF

32. A case of T2 N0 M0 with ER,PR + and her2neu - Is chemotherapy warranted ??

33. Genomic assays Onco type Dx 21 gene assay For pts with ER PR + and node negative Recurrence score is obtained Age > 50yrs and recurrence score >25 - chemotherapy Age >50yrs and recurrence score < 25 - endocrine therapy Age < 50 yrs recurrence score > 15 - chemotherapy Age < 50yrs recurrence score <15 - endocrine therapy

34. Other genomic assays Mammaprint - 70 gene assay Endopredict - 12 gene assay Prosigna - 50 gene assay

35. Radiotherapy - WBRT, APBI Indications Locally advanced breast carcinoma Positive lymph nodes Tumor >5 cm After BCS

36. Radiotherapy in BCS IF NEGATIVE LNs- WBRT + Regional node RT ( infra clavicular , supraclavicular , internal mammary and axilla if - central tumors >2cms , young age , extensive lymphovascular invasion In LN -ve - radiotherapy can be omitted if age >70yrs , ER+ve ,N0 If > 4 LN + — WBRT + regional nodal RT IF 1-3 LN + — WBRT + regional nodal RT ( can be avoided if T1-T2 , no preposterous chemotherapy , 1-2 + sentinel LN are present )

37. Harmonal based therapy Only used in ER,PR + pts Premenopausal Post menopausal There are 2 sources of estrogen :
Ovary
Peripheral conversion Only one source of estrogen :
Peripheral conversion The agents used are SERM as follows Tamoxifen duration 10 years , dose : 20mg/day Raloxifene Therefore the agents used are aromatase inhibitors
Eg..letrozole
Anastrozole
Exemestane
Duration - 10yrs

38. Side effects Premenopausal - hot flashes (most common ) - endometrial hyperplasia , patient to be monitored for endometrial lining every 3 months - increased risk of deep vein thrombosis Post menopausal -osteoporosis (most common )thus pts should undergo bone density evaluation to determine baseline bone density before administering aromatase inhibitors

39. A 55 ye old female with breast lump of size 8 cm with no skin involvement with 3 palpable lymph nodes in ipsilateral axilla ,BIRADS 4c, ER,PR- and Her2neu +

40. Case of T3 N1 M0 , locally advanced breast cancer ER PR - AND HER2NEU + Neoadjuvant chemotherapy MRM RADIOTHERAPY Harmonal therapy if ER PR + Her2neu targeted therapy

41. Neo adjuvant chemotherapy Indications - LABC Large tumor with pt desirous of BCS TNBC HER2NEU +

42. Her2neu directed therapy If a tumor is her2neu + ,her2neu directed therapy is given along with chemotherapy Drugs - tastuzumab - monoclonal Ab against extra cellular domain of HER2 receptor In combination - trastuzumab + neratinib - adjuvant chemo trastuzumab + lapatinib - metastatic disease Conjugate - TDM1 - trastuzumab +emtansine - drug conjugate allowing her2neu targeted delivery of an antimobicrotubule agent

43. NACT IN HER2NEU + tumors 6 cycles of TCH - TAXANES + cyclophosphamide + herceptine 4 AC + 4 TH f/b H for 1 year

44. Radiotherapy - chest wall RT + Regional nodal RT Total mastectomy with negative nodes tumor <= 5cm and margins >= 1mm - no RT TOTAL MASTECTOMY + tumor <5cm and margins <=1 mm - RT if central /medial tumor with size >2cmand in high risk individuals like young age If margins are positive - consider RT if re excision can’t be done LN -ve but tumor >5cm - RT LN + - RT given

45. Case of breast lump in a 55 yr old female with osteolytic lesion in the L2 M1 Management is mainly palliative in nature as it cannot be cured , the only aim is to improve quality of life It can be either palliative chemo or palliative radiotherapy to bony metastasis Harmonal therapy if ER PR + If the patient is ER,PR+ with no visceral crisis ,or symptomatic disease HARMONAL THERAPY IS SUFFICIENT , otherwise give chemotherapy as well

46. Newer agents Palbociclib - used in ER PR + and Her 2 NEU - , given along with harmonal therapy Alpelisib - PI3K inhibitor ,used for metastatic ER PR + Olaparib - PARP inhibitor, in BRCA positive metastatic pts

47. Thankyou