¹Assistant Professor, Department of Radiation Oncology, Cama & Albless Hospital, Mumbai, Maharashtra, INDIA.

²Associate Professor, ³Professor, Department of Radiation Oncology, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, INDIA.

Email: ganeshthakur512@gmail.com

RESULTS

Table 1: Patient characteristics of primary disease at presentation

Table 2: List of prognostic factors of primary and recurrent disease affecting outcome

DISCUSSION

This is prospective study of women with breast cancer who were optimally treated either at Tata Memorial Hospital (TMH) or outside centre for primary breast cancer and presented to TMH with recurrent disease. In this study we evaluated various risk factors affecting outcome in women who presented with clinically suspected local or loco-regional recurrence (with or without distant recurrence) in 100 consecutive women with a primary diagnosis of nonmetastatic breast cancer treated, preferably treated at TMH, Mumbai. The overall and disease-free survival was analyzed for different prognostic factors as shown in Table 2. It has been reported that disease free interval (DFI) before a LRR is a strong prognostic factor for overall survival and women with longer DFI have longer survival. Besides the DFI, age and surgical removal of the recurrence were significantly associated with survival after recurrence. DFI as a prognostic factor was reported by Annemieke et al.¹³ After adding covariables in the multivariable analysis, length of the DFI before a LRR remained of significant influence on survival after the LRR, which suggests that it is an independent prognostic factor. Patients with a short DFI and a LRR show on average less differentiated cells (grade III) and a larger primary tumour compared to the patients with medium and long DFIs, which suggests a more biological aggressive form of breast cancer. Moreover, short DFIs are significantly associated with subsequent distant metastases. Consistent with previous studies, good differentiation of the tumour cells (grade I, II), smaller tumour size, negative lymph nodes, positive hormone status, no axillary lymphnode dissection, radiotherapy and surgical removal of the recurrence have been identified to be associated with better survival. Both chemotherapy and hormone therapy are known to have a positive influence on survival after primary breast cancer. Yet after adding covariates in the proportional hazards models chemotherapy and hormone therapy was not of significant influence on survival after a LRR in the study by Annemieke et al. In the univariable analysis women who received chemotherapy or hormone therapy showed worse survival compared to those without recurrence of the breast cancer, possibly even during the adjuvant treatment period, might suggest resistance to the treatment. Of the total 100patients with a LRR, 69 patients not receive surgery for their recurrence. Typical reasons for withholding from surgical treatment include diffuse infiltration, inflammatory changes, subsequent DM, high age or patient preference. LRRs show differences in characteristics and prognosis and therefore need an individualized approach. In the current study, we showed that various clinic-pathological risk factors of the primary tumor such as clinical stage, clinical and pathological nodal status, lymphatic invasion and perineural invasion affected DFS as well as OS after re-treatment of the LRR. Amongst the initial treatment variables for the primary diagnosis, none of the surgical, radiation or systemic therapy related factors affected outcome after retreatment. Women who had received regional nodal irradiation primarily to the supraclavicular fossa had improved outcome. Similarly, RT boost to primary tumor bed also reduced the chance of LR. Similarly, patients presenting with only local or regional recurrence had better OS and DFS in comparison to those who had both. Women who are treated with curative intent had better OS and DFS in comparison with patients who are treated with palliative intent. The current study accrued women with LRR who were treated at variable time points. Overall, of all the consecutive 100 patients, about two third (60%) had concurrent distant metastases. Hence these were treated with palliative intent and rest was treated curatively. Not only has the site of the recurrence but its size and number also provided important information about the risk of developing distant disease. Patients with recurrences <1 cm had a lower distant recurrence risk compared to patients with local recurrences >1 cm.¹³ Although this seems to point towards a potential benefit of early detection of local recurrence, it can also be explained by a different biological behaviour, associated with certain clinical and mammographic features that facilitate detection. In a study by Voogd et al.,¹³ prognostic factors were almost similar for patients with a local recurrence within three years after diagnosis of the primary tumor and the group with a recurrence-free interval of more than three years, except for the axillary nodal status of the primary tumor that was the only important factor. Many studies have been performed to distinguish the local recurrences associated with a good or a poor prognosis and to identify risk factors for the development of distant metastases. The question is whether optimal loco-regional therapy is sufficient treatment or should it be followed by systemic treatment, depending on the risk for distant relapse. There is currently no good evidence that adjuvant systemic treatment is effective in patients with local recurrence. In a recent Cochrane systematic review of three randomized-controlled trials comparing systemic the rapy versus observation for women with loco-regional recurrence following mastectomy or breast-conserving treatment who did not have previous or synchronous distant metastases, provided insufficient evidence for an improvement in the overall survival.¹⁴ However, when considering the available evidence for its effectiveness in primary breast cancer, adjuvant systemic (re-)treatment may be considered in patients with unfavourable prognostic factors. Local recurrence at or near the site of the original tumour, skin involvement, diffuse growth of recurrence, a short disease-free interval and an unfavourable initial tumour stage have been found to be predictors of a poorer prognosis in more than one study. Patients with a recurrence remote from the primary tumour appear to have a better prognosis than those with a recurrence at or near the site of the primary tumour. The most likely explanation for this finding is that the first group consists largely of new primary tumours, whereas the recurrences that are located at or near the site of the primary tumour are true recurrences, originating from tumour tissue not removed by the primary excision or radio-resistant clone. The distinction between a true recurrence and anew primary is not always a clear-cut case. In most studies, the diagnosis “new primary” was applied when the recurrence was located elsewhere in the breast, had a different histology.

CONCLUSION

Numerous prognostic factors affect survival after diagnosis of recurrence. These include clinical stage at primary diagnosis, nodal positivity, presence of lymphovascular invasion and perinodal extension as well as site/s of recurrence. The risk of recurrence must be evaluated on an individual basis and the treatment plan must consist of multimodal therapy which takes the individual tumor biology into consideration. As these patients need a multi-modality management, decision regarding choice of treatment should be taken in a multi-disciplinary tumor board meeting, taking into account the previous locoregional and systemic treatment, expected risk of recurrence, clinical benefit and toxicity of retreatment.

REFERENCES

1. Hortobagyi GN, de la Garza Salazar J, Pritchard K, Amadori D, Haidinger R, Hudis CA, Khaled H, Liu MC, Martin M, Namer M, O’Shaughnessy JA, Shen ZZ, Albain KS: The global breast cancer burden: variations in epidemiology and survival. Clin Breast Cancer 2005, 6: 391-401.
2. Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin2005, 55:74-108.
3. Priyashetty: World report, India faces growing breast cancer epidemic. Lancet Vol 379 pp 992-93 (accessed on March 17, 2014).
4. van Dongen JA, Bartelink H, Fentiman IS, et al. Randomized clinical trial to assess the value of breast-conserving therapy in stage I and II breast cancer, EORTC 10801 trial. J Natl CancerInst Monogr. 1992;(11):15-18. http://www.ncbi.nlm.nih.gov/pubmed/1627421.
5. Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N EnglJ Med. 2002;347(16):1227-1232.
6. Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347(16):1233-1241. http://www.ncbi.nlm.nih.gov/pubmed/12393820\nhttp://www.nejm.org/doi/pdf/10.1056/NEJ Moa022152.
7. Darby S, McGale P, Correa C, et al. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: Meta-analysis of individual patient data for 10 801 women in 17 randomised trials. Lancet. 2011;378(9804):1707-1716.
8. Fisher B, Anderson S, Redmond CK, Wolmark N, Wickerham DL, Cronin WM. Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer. NEngl J Med. 1995;333(22):1456-1461.
9. Wapnir IL, Anderson SJ, Mamounas EP, et al. Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in five National Surgical Adjuvant Breast and Bowel Project node-positive adjuvant breast cancer trials. J ClinOncol. 2006;24(13):2028-2037. doi:10.1200/JCO.2005.04.3273.
10. Dershaw DD, Mccormick B, Osborne MP. Detection of Local Recurrence After ConservativeTherapy for Breast Carcinoma.
11. Parmar V, Krishnamurthy A, Hawaldar R, Nadkarni MS. Breast conservation treatment in women with locally advanced breast cancer e Experience from a single centre. 2006. doi:10.1016/j.ijsu.2006.01.004.
12. Annemeike et al.:Survival after Locoregional Recurrence or Second Primary Breast Cancer: Impact of the Disease-Free Interval,PLOS ONE, DOI:10.1371/journal.pone.0120832 April 10, 2015
13. Voogd AC, van Tienhoven G, Peterse HL, et al. Local recurrence after breast conservation therapy for early stage breast carcinoma: detection, treatment, and outcome in 266 patients. Dutch Study Group on Local Recurrence after Breast Conservation (BORST). Cancer. 1999;85(2):437-446.
14. Rauschecker H, Clarke M, Gatzemeier W, et al. Systemic therapy for treating locoregional recurrence in women with breast cancer.Cochrane Database Syst Rev(4)., CD002195.