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Local Recurrence and Reconstructive Options Following Oncoplastic Breast Surgery
The management of recurrent breast cancer is a multidisciplinary challenge. Clinical and radiological follow-up of patients following breast cancer treatment aims to detect early locoregional and distant metastasis. Local breast recurrence represents the reappearance of cancer and can occur at or near the site of excision following breast-conserving surgery (BCS) or in the soft tissues of the anterior chest wall or skin flap following mastectomy. In the case of oncoplastic surgery, the majority of local recurrence appears at the initial site where the resection was performed.
The clinical presentation of a patient with a local recurrence may vary and includes a new lump or firmness within the operated breast, nipple inversion or discharge, as well as skin changes, for example, erythema, rash, firm nodules, oedema, tethering, or thickening of scar tissue ( Figs. 18.1 and 18.2 ). Differential diagnoses include postoperative fibrosis, fat necrosis, suture granulomas, benign breast disease, and post-radiotherapy skin changes. Persistent edema and erythematous skin overlying the operated breast should raise the suspicion of inflammatory recurrent breast cancer and warrants punch biopsy; however, this can be difficult to differentiate from mastitis and post-radiotherapy skin changes. Even rarer is cutaneous metastasis “en cuirasse” located on thoracic and abdominal walls characterized by infiltrated, hard, and sclerodermiform plaques.
Local recurrence following right breast oncoplasty demonstrating ulcerated nodules along the medial perimeter of the breast.
Local recurrence following right mastectomy demonstrating nodularity in the subcutaneous tissues around the mastectomy scar.
Mammography is the mainstay of surveillance imaging following BCS detecting 8–50% of ipsilateral recurrences, whereas ultrasound and magnetic resonance imaging remain supplementary surveillance modalities. Mammographic appearances of ipsilateral recurrence include new nondystrophic microcalcifications, a new mass compared with baseline mammogram, increased architectural distortion or opacity, and an increase in skin thickening after posttreatment changes have subsided. Not all local recurrences will be associated with mammographic change, and a normal mammogram does not exclude local recurrence. Stereotactic and core biopsies histologically confirm the diagnosis of local recurrence.
Local recurrence rates following surgery vary widely in the literature due to differences in patient cohort selection, extent of surgery, and use of adjuvant therapies. The incidence of local recurrence after BCS and radiotherapy ranges from 10–22% at 10 years and, after mastectomy, ranges from 5–15% at 10 years. The median time to recurrence is 3–4 years for BCS and 2–3 years for mastectomy. Breast recurrence is a predictor of distant metastasis and decreased survival. A meta-analysis by the Early Breast Cancer Trialists’ Collaborative Group demonstrated a negative effect of a local recurrence on survival. In 5–15% of cases, local recurrence is associated with concomitant regional and distant metastasis; therefore, computed tomography and positron emission tomography staging is considered for all patients with confirmed local recurrence.
The a etiology of local recurrence remains unclear; however, theories include incomplete excision of the primary tumor, unrecognized multifocal disease, entrapment of tumor cells within obstructive lymphatics, and local implantation of systemic circulating cells. In the context of local recurrence alone, excision surgery and adjuvant therapies have curative intent. For patients presenting with local recurrence and distant metastasis, a multidisciplinary approach will be required to assess the need for palliative resection of the local recurrence as an adjunct to systemic treatment.
Determinants of Local Recurrence
The importance of negative margins in BCS cannot be overstated, and positive margins are a risk factor for increased local recurrence. Positive margins according to the joint guidelines of the American Society of Breast Surgeons/Society of Surgical Oncology/American Society of Radiation Oncology constitute “ink on tumor” for invasive breast cancer and less than 2 mm margins for ductal carcinoma in situ. Current UK guidelines from the Association of Breast Surgery consensus define positive margins as 1 mm for both invasive and ductal carcinoma in situ. A systematic review on oncologic reporting in BCS highlighted variation in the frequency of margin involvement (0–36%) and local recurrence rates of 0–10.8%. Positive margins (ink on invasive or ductal carcinoma in situ) are associated with a twofold increase in the risk of ipsilateral recurrence compared with negative margins. More widely clear margins than no ink on tumor do not significantly decrease the rate of recurrence compared with no ink on tumor even in high-risk groups with unfavorable biology. Local recurrence is influenced more by tumor biology and therapy than surgical margin. Young age at diagnosis (less than 40 years) is a significant risk factor for local recurrence at 5 years with a relative risk of 2.21 (95% CI 1.62–3.02). Body mass index gain following BCS is also significantly associated with higher rates of recurrence.
Pan et al performed a meta-analysis of the results of 88 trials involving 62,923 women with estrogen receptor (ER)-positive breast cancer who were disease-free after 5 years of scheduled endocrine therapy. The risk of disease recurrence, both locally and distant, was strongly correlated with the original TMN classification (tumour, node, metastasis) status and tumor grade. During the study period from 5–20 years, the absolute risk of local recurrence with T1N0 ER positive breast cancer or a contralateral breast cancer were low grade 17%, moderate grade 22%, and high grade 26%. Tumor grade and size are significant predictors of recurrence after adjustment to other variables.
Breast tumors can be divided into subtypes based on molecular profiling, particularly those differing in proliferation. Measurement of the level of activation of the proliferation pathway is via Ki-67 expression. Ki-67 is a nuclear protein associated with cellular proliferation. Immuno-staining can assess the percentage of breast cancer cells expressing Ki67 (<14%; >14%). Molecular subtypes of breast cancer include luminal A (ER-positive or progesterone receptor [PR]-positive and Ki-67 < 14%); luminal B (ER- or PR-positive and Ki-67 ≥ 14%); luminal human epidermal growth factor receptor 2 (HER2) (ER- or PR-positive and HER2-positive); HER2-enriched (ER-negative, PR-negative, and HER2-positive); and basal-like (ER-, PR-, and HER2-negative, triple negative). Luminal B, HER2 positive, and triple negative subtypes all show significant increased risk for both local recurrence and distant recurrence following BCS. Five-year local recurrence rates following BCS and radiotherapy for each subtype have been reported: 0.8% for luminal A, 2.3% for luminal B, 1.1% for luminal HER2, 10.8% for HER2-enriched, and 6.7% for triple-negative disease. Similarly, after mastectomy, patients with luminal A tumors had the lowest rates of local recurrence, 8% at 10 years. Gene expression profiling by microarray analysis is being used to identify gene expression profiles that can predict local recurrence. Although still being refined, researchers have been able to identify subgroups of patients at increased risk of developing local recurrence following BCS.
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