LABC ( Locally advanced breast cancer ) occurs at first presentation in about one-fifth of breast cancer patients worldwide, with lower incidence in countries with established screening programmes but as high as 60% in some other countries. Usually, the definition of LABC includes large operable primary breast tumours ( stage IIB, IIIA ) and/or those involving the skin or chest wall and/or those with extensive lymphadenopathies ( stage IIIB, IIIC ). For the purpose of advanced breast cancer guidelines, the Consensus Group define LABC as inoperable locally advanced disease that has not yet spread to distant sites.
Inoperable LABC is a heterogeneous designation encompassing a range of clinical situations from neglected low-grade ER-positive breast cancers to rapidly progressing usually ER-negative disease.
A more homogenous form of LABC is inflammatory breast cancer ( IBC ), a distinct clinic–pathologic entity. Inflammatory breast cancer has a greater association with younger age at diagnosis, higher tumour grade, and negative estrogen receptor ( ER ) status.
The first steps in the management of this disease are a core biopsy to provide histology and biomarker assessment ( including ER, PR, HER-2, and proliferation/grade ), and a full staging workup. Due to a relatively high risk of distant metastases, thoracic and abdominal CT scans are preferred to thorax X-ray and liver ultrasound, and a PET–CT is also an acceptable option.
A multimodality approach is key for locoregional control and survival, including systemic therapies, surgery, and radiation. The type of systemic therapy is similar to the one used in the (neo)adjuvant setting, with anthracycline and taxanes as the backbone of the chemotherapy regimes.
For HER-2-positive LABC, anthracyclines should not be administered concurrently with Trastuzumab since this approach does not increase the pCR rate, and it could increase the risk of cardiac toxicity, based largely on studies in the metastatic setting.
For luminal-like LABC, initial treatment options include chemotherapy ( with sequential anthracyclines and taxanes ) and endocrine therapy, depending on tumour ( grade, biomarker expression ) and patient characteristics ( menopausal status, performance status, comorbidities ) and preferences. A number of studies have demonstrated significant activity of endocrine therapy, particularly in luminal A-like disease. Data presented after ABC2 strongly suggest that this subset of breast cancer, especially lobular histology, is less sensitive to chemotherapy ( at least in terms of pCR rate ). Very few data exist on primary endocrine therapy in premenopausal women and, therefore, it cannot be recommended outside of clinical trials.
Primary systemic therapy in inoperable LABC allows breast-conserving surgery in variable percentages depending on tumour/patient characteristics.
Mastectomy remains the only option before or after radiotherapy for those patients not amenable to breast conservation and for all patients with inflammatory breast cancer.
For the time being, axillary dissection is still standard of care in inoperable LABC.
As for all other stages of breast cancer, decision-making at a multidisciplinary tumour board is highly recommended.
Source: ESO ( European School of Oncology ) and ESMO ( European Society of Medical Oncology ) Guidelines, 2014