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Advanced breast cancer: specific sites of metastases


Due to the lack of prospective randomized data for the management of liver metastases from breast cancer, and the existence of several locoregional techniques, local therapy of liver metastases should only be considered in highly selected patients. Each case should be discussed with a multidisciplinary tumour board, before a decision is made. Inclusion in a clinical trial, when available, is considered the best option.
When breast cancer recurs only on the chest wall after mastectomy, the use of intensive local–regional therapy should be considered.
Therapy can include surgical excision alone, surgical excision followed by radiation therapy, radiation therapy alone ( when surgical excision is not feasible ), or concurrent chemotherapy and radiation.
Complete surgical resection reduces the total required dose of radiation therapy and also maximizes the likelihood of long-term disease control.
Complete excision alone can lead to a 5-year disease-free survival rate of 35%. Complete resection followed by locoregional radiotherapy results in a 5-year local–regional control ranging from 60% to 77%.

Long-term predictors of disease-free survival after a local–regional recurrence include a disease-free interval of greater than 24 months and a complete excision.

With modern radiotherapy techniques, it is often possible to re-irradiate with full dose without too many side-effects. The first results of retreatment with stereotactic body radiotherapy techniques have been published recently, describing promising local control rates.

Concurrent chemoradiation has both preclinical rationale and clinical efficacy in many solid tumour types. Potential mechanisms of chemotherapy and radiotherapy interactions include increasing radiation damage, inhibition of DNA repair processes, enhanced activity against hypoxic and radioresistant cells, and prevention of regrowth of tumour after radiation.
In patients who have received prior radiation, chemoradiation can be considered, as the residual tumour should be considered radioresistant unless combined with a potentiating agent, provided that the patient is judged a candidate and can tolerate additional radiation therapy.
Agents having shown potential synergy with radiation include Platinum analogues, anti-metabolites, and taxanes.
Several novel therapeutics are also being studied in the trial setting in combination with radiation, including EGFR inhibitors, HER-2 inhibitors, and poly (ADP-ribose) polymerase inhibitors.

Patients who have residual isolated local–regional recurrence after attempted resection, or minimal systemic disease, might derive benefit from consideration of this multimodality approach.

Hyperthermia has a proven benefit for the treatment of superficial malignancies, acting as a radiosensitizer. Trials evaluating the role of hyperthermia in combination with radiotherapy in patients with chest wall recurrences have shown a significant improvement in complete response rates with the addition of hyperthermia, especially in previously irradiated patients ( e.g. complete response: 24–31% in the no-hyperthermia arm versus 57–68% in the hyperthermia arm ).
However, there was no difference in survival between the two treatment arms.
Recent studies have analysed the combination of radiotherapy, hyperthermia, and concurrent chemotherapy in this patient population.

Finally, systemic therapy ( both endocrine and chemotherapy ) has been shown to benefit patients after complete resection of a first locoregional isolated recurrence.
The CALOR study, a randomized phase 3 study, allocated to 162 patients to either physician's choice chemotherapy or no chemotherapy.
The use of chemotherapy after surgery resulted in a significant reduction in systemic recurrence ( hazard ratio, HR 0.59; P = 0.046 ).
In the subgroup of patients with ER-negative tumours, there was also a significant improvement in survival. This study provides important data in support of use of systemic chemotherapy after surgical resection of isolated locoregional recurrence of ER-negative breast cancer. ( Xagena )

Source: ESO ( European School of Oncology ) and ESMO ( European Society of Medical Oncology ) Guidelines, 2014

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