Locally Advanced Breast Carcinoma

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Prof. P. N. Agarwal Locally Advanced Breast Carcinoma

What is LABC ? • Bulky primary breast tumors and/or extensive adenopathy • Includes T3/T4 & N2/N3 disease. • Now includes isolated supraclavicular metastasis • 6% of CA breast in US presents as Stage III disease. • In review of CA breast pts. in LNJP, >60% pts. presented as LABC

Diagnostic Work Up • Fine needle aspiration cytology • Core biopsy - to confirm invasion, ER/PR & Her-2-Neu status • Diagnostic open biopsy if core biopsy nondiagnostic • Punch biopsy if skin involvement • If adenopathy, FNAC of L.N. for staging

Diagnostic Work Up (contd.) • Bilateral Mammography - multicentric disease is a contraindication to BCT • Axillary USG - for nodal status & image guided FNA (20% false negative results).

Metastatic work up • Baseline bone scan • Chest, abdomen & pelvic CT scans are recommended for detection of metastasis • Directed radiographs to sites of new bone pains. • CT head for new neurological symptoms. • Yield in early CA breast is 2-3% but in LABC it is 30%

Evolution of Treatment • Haagensen & Stout - radical mastectomy in LABC led to dismal results • Reported 5 yr local recurrence & survival rates of 46% & 6%. • They defined inoperable LABC Extensive breast skin edema/satellitosis, Intercostal/parasternal nodules, Arm edema, Supraclavicular metastasis, or

Evolution of Treatment • Therapeutic doses of chest wall irradiation also gave poor results- 5 yr local recurrence rates 46-72% & survival 16-30% • Combined treatment with radiation + surgery also failed.

Chemotherapy • Neoadjuvant / Induction chemotherapy revolutionized LABC care. • Early concerns were - surgical complication rate, prognostic value of axillary staging & overall survival after delayed surgery. • It has been shown that neoadjuvant therapy does not worsen survival but improves resectability.

Optimum Pre-op. Chemotherapy • NSABP - 27 study preliminary results reveal pCR of 26% with addition of docetaxel. • The Aberdeen trial compared 8 cycles of chemotherapy - Doxorubicin based ( pCR 16%) and Doxorubicin + docetaxel ( pCR 34% ).

Optimum Pre-op. Chemotherapy • Optimal chemotherapy for CA breast consists of 4-8 cycles of chemotherapy with 2 of major drugs ( Doxorubicin + Taxanes) included in each cycle. ( Bull Cancer 2006 Nov1;13(11):1121-9 ).

Current Treatment • Currently, optimal control is achieved with preoperative chemotherapy followed by surgery & radiotherapy. • Doxorubicin based CT is the most widely used induction regime. • 30% pCR has been reported with preop. Doxorubicin, Cytoxan, 5-FU & weekly Taxol.

Rx approach

Component 5 yr local 5 yr survival s recurrence

Single modality

Surgery

46%

6%

XRT XRT  Sx Sx XRT CT  Sx CT  XRT Sx  CT CT  Sx  XRT

50% 70% 70% 18% 36% 20% 5-9%

35% 30% 32% 49% 35% 65% 64-89%

Dual Modality

Triple Modality

Sx CT  9% XRT

66%

Hormonal Therapy • Neoadjuvant endocrine therapy for ER+ LABC is also an active area of research. • 3- 4 months of therapy are preferred for an adequate response assessment • Aromatase inhibitors like Letrozole are more effective than Tamoxifen.

Breast Conservation Therapy • Criteria for BCT in postneoadjuvant LABC: • Patient desire for breast preservation • Absence of multicentric disease • Absence of diffuse microcalcifications • Absence of skin involvement consistent with inflammatory breast cancer • Residual tumor mass amenable to a marginnegative lumpectomy resection

BCT (contd.) • Several prospective RCTs have confirmed acceptable rates of local recurrence among LABC pts undergoing BCT after NACT. • The NSABP B-18 investigators did note a trend toward higher local recurrence rates among patients requiring preoperative downstaging in order to become lumpectomy eligible (15% versus 7%).

Immediate Breast Reconstruction • LABC traditionally has been perceived as a contraindication to IBR. • Newman found no adverse effects on surgical complication rate / adjuvant chemotherapy • IBR with implants was associated with more RT related complications, nearly half necessitating removal of implants.

IBR (Contd.) • Delayed reconstruction is usually preferred in LABC as PMRT is mostly required. • For extensive chest wall defect at mastectomy, LD flap is the most common approach - provides durable, radiation tolerant coverage.

Locoregional Irradiation • Pts. who have at least 4 metastatic lymph nodes • 5 cm of residual disease in the breast after chemotherapy • All lumpectomy patients require breast irradiation

PMRT (Contd.) • A conservative approach is to recommend radiation to all patients that present with LABC • However, patients with little or no residual breast/axillary disease after chemotherapy may not derive a significant benefit from regional nodal irradiation • Existing data is limited in this aspect.

Postoperartive Systemic Therapy • Hormone receptor positive breast cancer should receive at least 5 years of either tamoxifen or an aromatase inhibitor • Aromatase inhibitors given only to postmenopausal females • Tumors overexpressing HER2/neu require adjuvant Trastuzamab

Locoregional recurrences • Chest wall recurrence is a grave event indicating aggressive tumor biology. • Managed with aggressive resection • 5 yr survival was 35% - 47%

Standard Of Care • Presently, the standard therapy is NACT followed by surgery ( mastectomy/BCT ) and PMRT & endocrinal therapy as indicated in a particular case. • This has led to 5 yr. local recurrence rate of 5 - 9% and survival of 64 - 89%.

Overall survival curves for patients with inflammatory breast cancer undergoing combined modality treatment according to whether a pathologic complete response (Path CR) was achieved based on the pathologic findings at the time of mastectomy. Int J Radiat Oncol Biol Phys 2003;55:1200.

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