Recurrences can happen at any time, even more than 10 years post initial treatment. The development of recurrence after primary treatment of breast cancer is life-limiting. All patients should be followed initially at 3-4 month intervals, then after 2 - 2.5 years at 6 month intervals until 5 years post-treatment, and then at least annually. All patients should be restaged comprehensively at time of identification of recurrence for distant metastatic disease. Local recurrence should be biopsied to confirm disease and re-evaluate ER/PR/HER2/neu receptors. Treatment strategies should be based on the individual characteristics of the disease and patient.
Mastectomy is the standard salvage treatment. Most women with breast conservation and recurrence have been treateed with RT in the initial approach. Re-irradiation following first course carries a substantial risk of serious late effects. Grade 2-3 late complications range from 0% - 32% depending on dose (cummulative dose and second treatment dose). Radiation the second time also appears to be less effective with a study by Deutsch using limited volumes to 50 Gy resulting in second recurrence rates of 23%. Resch used pulse rate brachytherapy in partial breast RT after repeated lumpectomy and noted a second recurrence in 5/17 cases. In very highly selected cases, with a median followup of 60 months.
Patients are also at risk of axillary nodal metastases. If the original treatment was SNB then the patient with recurrence should proceed to full axillary node dissection.
Patients with recurrence after initial mastectomy have worse prognosis than after initial breast conservation therapy. In Canadian and Danish prospective studies examining post-mastectomy radiation (PMRT), patients who developed local-regional recurrences had very high rates of development of metastatic disease after an isolated recurrence at 73%. The rate of distant metastases was no different with or without PMRT.
The most common site of local recurrence was in the chest wall and supraclavicular lymph nodes. Combined EORTC 10801 and Danish 82TM trials, are the basis for recommendations for treatment of patients experiencing a local only recurrence. This analysis compared Breast concerving therapy with mastectomy in Stage I/II disease. 8% experienced a local recurrence as an initial event. These patients were divided into mastectomy and BCS about equally. 76% of the mastectomy group were able to undergo radiation (no prior radiation to the chest) with or without surgery as treatment for locally recurrent disease. No survival difference was found when patients receiving salvage treatment were compared wiht 50% of both groups alive at 10 years.
Comprehensive restaging is indicated in recurrence as distant metastases are common and will influence treatment decisions. CT of the chest/abdomen and pelvis and if symptomatic an MRI of the brain are reasonable. Where bone metastases are suspected, a bone scan or SPECT scan are reasonable as is a PET/CT. Appropriate laboratory studies include CBC, Chemistry and Liver function tests. The site of recurrence should be biopsied directly and redeterminations of receptors, HER2/neu should be performed to determine any histological changes.
Katz, et al (JCO 2000;18:2817-) analyzed 1031 patients treated with mastectomy and Adriamycin based chemotherapy to define groups benefiting from post-mastectomy radiation therapy. These groups are those with tumor > 4 cm, or extranodal extension ≥ 2 mm who experienced local recurrence rates in excess of 20%.
Patients with tumor ≥ 4 cm or at least 4 nodes positive should receive PMRT. Patients wiht 1-3 nodes positive should strongly consider radiation. If there are large tumors, extranodal extension or minimal axillary dissections, there are higher rates of local-regional recurrence and these patients may benefit from PMRT.
Locally recurrent mastectomy treated patients should undergo surgical resection of the local recurrence if possible. This shold be followed by involved field radiation therapy to the chest wall, supraclavicular area if radiation therapy can be safely administered. The goal of surgery is to obtain clear margins and implies limited extent of recurrence. Unresectable disease should be treated with radiation, presuming no prior radiation was administered. After local/regional management, women should be considered for adjuvant systemic chemotherapy. The NCCN emphasizes the importance of individualizing treatment strategies in patients with local-regional recurrence.
Any planned radiation must incorporate in decision making the nature and extent of prior radiation if any, and sensitive and critical structures including the brachial plexus, heart, skin and ribs.
All radiation fields should be planned using 3d conformal techniques and should incorporate techniques for tissue compensation to insure uniformity of dose to the chest wall and supraclavicular regions. the chest wall, level II-III axillary nodes should be treated.
Early recurrence is a worse prognostic indictor. An interval recurrence at < 2 years indicates worse outcomes than those with late recurrences. Early recurrences may be the result of early repopulation while late recurrences may be a new primary (or so it is thought based on Yale and MD Anderson histologic indicators in late second primaries).
For Post-mastectomy patients, the Danish 82b/c trials concluded based on multi-variate analysis the following prognostic indicators are associated with poorer outcomes:
Patients who have previously been treated with mastectomy alone who have a resectable chest wall recurrence have greater probability of disease control and improved outcome. MDACC found that initial node status, time to recurrence and availability of radiation to treat the recurrence were important independent predictors for favorable outcome after chest wall recurrence. When none of these factors are present (few cases) the OS5 was 86% and the median survival was 141 months. With one or two unfavorable indicators OS5 was 48% and median survival 54 months. With 3 unfavorable factors, the OS5 was 0% and median survival was 16 months. The outcome was as poor for patients originally with T1/2 1-3 nodes positive as it was for nodes ≥ 4 positive. N0 patients did better.
MDACC recurrence unfavorable prognostic indicators:
Prognosis based on number of factors present:
| Factors Present | OS5 | Median Survival |
|---|---|---|
| 0 | 86% | 144 months |
| 1-2 | 48% | 54 months |
| 3 | 0% | 16 months |