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Advanced breast cancer

Advanced breast cancer. Dr.sabarinath menon. Locally advanced breast cancer Metastatic breast disease recurrence.

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Advanced breast cancer

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  1. Advanced breast cancer Dr.sabarinath menon

  2. Locally advanced breast cancer • Metastatic breast disease • recurrence

  3. A 60 year old female presents in the out patient clinic with c/o mass in Rt breast & vague pain. On examination Rt breast has a hard mass of size 6 x 4 cm with fixed lymph node in the axilla. A mammogram was done which showed the presence of hyper dense spiculated mass in the breast. FNAC came as infiltrating ductal carcinoma.

  4. What is the stage of the disease? • T3 N2 M0 • She is suffering from LABC

  5. Locally advanced breast cancer • Presence of tumor > 5 cm in size • Associated with or without skin or chest involvement • With fixed axillary lymph node/ipsilateral int.mammary LN / supraclavicular LN • In the absence of any evidence of distant metastasis

  6. LABC includes which all stages • Stage II b , III a , III b , III c (AJCC)

  7. II b - T2 N1 M0 - T3 N0 M0 • III a - T0-2 N2 M0 - T3 N 1-2 M0 • III b -T4 N 0-2 M0 • III c - any T N3 M0

  8. How will u work up the case ?

  9. Mammogram. • Why do u want a mammogram ?

  10. Diagnostic • Base line mammogram is must in LABC. • What r u looking for in a mammogram ?

  11. Mass lesion* • Architectural distortion* • Asymmetric densities • Micro calcifications • What should be the next step?

  12. FNAC • tru-cut biopsy

  13. Next step will be to rule out metastasis routine investigations • CBC , LFT , C-X – Ray if symptomatic • Skeletal roentgenologic survey • USG / Abd CT if LFT elevated or if hepato splenomegaly present • Radionuclide bone scan • CT/MRI brain if CNS symptoms present

  14. Other investigations • Hormone receptor status • Her 2 /neu expression

  15. How to manage a case of LABC ? • What all options do we have ?

  16. Surgery tackles the disease head on • Radiotherapy to prevent loco-regional recurrence • Systemic therapy to treat systemic spread

  17. Evolution of treatment for breast cancer • From unimodal Rx to multimodal Rx • From radical to conservative

  18. William halsted described radical mastectomy at the end of 19th century • Mid 20th century MRM was born* • Breast conservative surgery is now increasingly being preferred.

  19. Radiotherapy evolved from radical-en –block radiation to radiation as an important adjunct to surgery • Chemotherapy evolved from 12 cycles CMF regime to 6 cycles • The use anthracyclines to introduction of taxanes • The success story of NACT

  20. What is NACT ? • Neo adjuvant chemotherapy • What is the rationale of using NACT ?

  21. LABC patients present with relatively high burden of micrometastasis & hence it makes sense to initiate systemic therapy upfront at the earliest

  22. Advantages of NACT • Early initiation of systemic Rx • Inhibition of post surgical growth spurt • Delivery of chemotherapy through intact tumor vasculature • In vivo assessment of response • Down staging of primary tumor & lymph node metastasis • Feasibility of BCT

  23. Disadvantages • Local Rx of non responders could get delayed • Risk of drug resistance • Inaccurate pathological staging • ? Increased risk of surgery &radiotherapy related complication

  24. How to assess the effectiveness of NACT? *physical examination *mammograph *ultrasound • 10 – 30% 0f patients show cCR • 50 – 60% of patients show partial response • Only 1/3rd of patients of patients with complete cCR have pathological complete response

  25. Which are the chemotherapeutic agents being used? • Anthracycline based chemo is now considered to be most effective • Addition of taxanes (paclitaxel / docetaxel) has increased the efficacy • CMF is also being used.

  26. Number of neoadjuvant cycles required? • Either 3-4 cycles • Chemo continued up to maximal response*

  27. Is there a role for neo adjuvant hormonal therapy? • Use of estrogen ( diethylstilbesterol) results in hormonal synchronization of tumor cells • Better response rate • But no survival benefit

  28. The patient was treated with NACT.her tumour completely shrunk & axillary lymph nodes disappeared. How to proceed?

  29. Surgery • Radiotherapy • Surgery + radiotherapy

  30. Surgery for LABC • Modified radical mastectomy* • Breast conservative treatment wide local excision lumpectomy

  31. In all cases of LABC axilla has to be treated. • Either axillary dissection or axillary radiation • If axillary dissection better to do level III clearance*

  32. BCT in LABC • In patients with cCR with pathological complete response radiation may be given • In rest WLE / lumpectomy • Patient preference is important • Residual tumor should be less than 5 cm • Resolution of skin edema • Absence of microcalcification • No evidence of multicentricity

  33. Radiotherapy alone was tried after NACT but loco-regional recurrence rate was found to be high

  34. So we treated the patient with MRM. What next ?

  35. Adjuvant chemotherapy • Anthracycline based regime (AC / CAF) • 4 – 6 cycles • Has better response in c-erb B2 +ve cases • addition of taxanes improve response • CMF is used only in c-erb B2 –ve cases known cardiac problem

  36. CMF “classic” – 6 cycles every 28 days • CMF “i.v” – 8 cycles every 21 days • CAF – 4 to 6 cycles every 28 days • AC – 4 cycles every 21 days • AC – T - AC 4 cycles followed by paclitaxel every 21 days

  37. Radiotherapy • Post operative radiotherapy is must • radiotherapy technique 1. whole en bloc radiation 2. loco regional radiation

  38. Whole en bloc technique radiation is delivered by two tangential fields encompassing the whole breast • The medial border is 2 cm on the opposite side from 1st or 2nd intercostals to 2 cm below the inf mammary line • The lateral border is mid axillary line • Treatment planning is done with the help of CT • Advantage – there is no hot & cold spots • Disadvantage – less dose above the clavicle

  39. Loco regional radiation • Set of separate fields 1. breast or chest wall 2.ipsilateral axilla/supra & infra clavicular field 3. internal mammary nodes*

  40. Indication for axillary radiation • 4 or more axillary lymph node positive • Extra nodal disease • Inadequate axillary clearance or residual disease • Unknown axillary status

  41. Hormonal therapy • Albert schnieger of Germany recommended oophorectomy in premenopausal women with ca breast • In 50’s adrenalectomy and hypophysectomy was recommended • 1973 - McGuire demonstrated the presence of estrogen receptors • 1975 – Horwitz identified progesterone receptors • then studies with tamoxifen began

  42. Anti estrogens • Tamoxifen & analogues - torimefine - droloxifene - idoxifene • Pure anti estrogens • Targeted anti estrogens - raloxifene

  43. Tamoxifen (nolvadex) • Still considered the first line hormonal Rx • Results in reduction in annual recurrence rate • It reduces the incidence of contralateral breast cancer • Acts by blocking estrogen stimulation of cancer cells / inhibits conversion of estrone sulfate to estradiol / production of TGF which inhibits growth of tumor cells regardless of hormonal status

  44. Indications • All women with breast cancer & +ve LN • Tumor greater than 1cm & ER +ve • Tumor < 1cm & ER –ve , tamoxifen may be given as the benefits outweigh the risk

  45. Dosage is 20 mg od for 5 years • Disadvantages • Endometrial ca * • DVT & pul embolism • Cataract • Hypercalcemia • Nausea , hotflushes

  46. Newer anti estrogens • Tormifene (chlortamoxifen) less potent & has weak estrogen like property in post menopausal women • Droloxifene (3-hydroxytamoxifen) shorter half life , more binding capacity , prevents osteoporosis

  47. SERM • Selective estrogen receptor modulator • Raloxifen • It has estrogenic effect on bone & cvs • Anti estrogenic action on breast

  48. Aromatase inhibitors • Aromatase enzyme is the rate limiting step in estrogen bio synthesis • Aminogluthemide – used in premenopausal women. results in medical adrenalectomy. • Selectivearomatase inhibitor – anastrazole , letrazole , formestane , examestane etc. used in post menopausal women

  49. LHRH agonist – goserline , luperolid alternative for surgical oophorectomy • Additive hormonal therapy progestrin – megestrol estrogens , androgens etc

  50. The new silver bullet • Trastzumab (herceptin) • Only 25 % of patients are Her-2/new +ve • They have increased growth rate & increased risk of metastasis • Trastuzumab is a re-combinant mono-clonal antibody that acts on the receptor • Decreased local recurrence rate & increased disease free survival has been noted

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