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Locally advanced breast cancer (LABC)

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Defined as: a primary lesion greater than 5 cm, inflammatory breast cancer, with skin or chest wall invasion, or with fixed axillary lymph node involvement.

Account for about 6%-10% of breast cancers presenting as stage III disease with a 5-year survival rate of 50%.

Poor prognostic lesion treated with neoadjuvant chemotherapy followed by mastectomy and chest wall radiation.

Preoperative chemotherapy associated with an increased rate of breast conservation surgery compared to postoperative treatment.

Standard of care for LABC is neoadjuvant chemotherapy.

LABC includes clinical stages IIA, IIB & IIIA.

Goals of preoperative chemotherapy are: to down stage the disease so as to render breast conservation feasibility, to eradicate disease in axillary lymph nodes and to allow testing of tumor drug sensitivity, all to improve the prognosis.

HER2 positive breast cancer is present in approximately 20% of early breast cancer and 35% of locally advanced breast cancers, and has been associated with the poor prognosis.

Preoperative chemotherapy not associated with an increase in survival.

Neoadjuvant studies demonstrate that chemotherapy is associated with a higher five year overall survival and disease free survival in patients achieving pathologic complete response compared with those who do not, with overall survival 89% versus 64% and disease free survival 87% versus 58%, respectively (Kuerer HM et al).

In patients with HER2 positive disease neoadjuvant therapy should include HER2 to targeted therapy plus chemotherapy.

Higher survival rate for women less than 50 year of age when treated with preoperative chemotherapy.

Higher ipsilateral recurrence rate in women younger than 50 year among women receiving preoperative chemotherapy.

A complete pathologic response (pCR) after preoperative chemotherapy is a strong prognostic marker with 85% of women surviving with a pCR compared to 73% survival for women with residual pathologic disease at nine years follow-up.

Pathologic complete responses with neoadjuvant chemotherapy range from 7-36%.

Pathologic in breast response to preoperative chemotherapy generally correlates with pathologic response in axillary lymph nodes.

Higher rates of local/regional recurrence after neoadjuvant chemotherapy associated with >2cm residual tumor, multifocal residual tumor and lymphovascular invasion.

The addition of postoperative radiation following neoadjuvant chemotherapy and mastectomy reduces local recurrence rate and may improve disease-specific survival in patients with 4 or more positive lymph nodes.

Only 2-3% of patients treated with neoadjuvant chemotherapy show signs of progressive disease.

Surgical resection essential to evaluate chemotherapy response and achieving durable locoregional control.

Isolated supraclavicular metastases stage III/LABC disease.

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