Isolated Supraclavicular Recurrence of Breast Cancer

Abstract & Commentary

Synopsis: The development of an isolated supraclavicular node recurrence of breast cancer after primary surgical resection (including axillary node dissection) was found, upon review of the tumor registries of 8 community hospitals in The Netherlands, to occur very uncommonly (less than 1%). Examination of clinical outcomes for these patients indicates that isolated supraclavicular recurrence is an antecedent of disseminated disease, in that, even with local control (as achieved by radiation therapy), the great majority of patients soon develop systemic disease.

Source: van der Sangen MC, et al. Cancer. 2003;98: 11-17.

The optimal treatment for women who recur with breast cancer in an ipsilateral supraclavicular node without other evidence for distant metastases remains unclear. It is established that women who present with supraclavicular adenopathy develop distant metastases and have a shorter survival than women who present with axillary nodes alone.1 However, the same cohort—women with supraclavicular nodes at presentation—do fare better than those who present with metastases to distant organs.

In the current report, the experience from 8 community hospitals in the southeastern part of The Netherlands is reported. During an approximate 10-year span, 4669 patients with invasive breast carcinoma underwent axillary lymph node dissection in these hospitals, and follow-up revealed that 42 patients (approximately 1%) developed isolated supraclavicular recurrence without other clinically evident sites of distant metastases. A review of these patients, their therapy, and their clinical course is the subject of this report.

The median interval between treatment of the primary tumor and the diagnosis of supraclavicular recurrence in these 42 patients was 2.5 years (range, 0.2-11.5 years). Radiotherapy was administered to 25 patients (60%), 5 of whom also underwent surgery and 16 of whom also received chemotherapy or hormonal therapy. Eleven patients received hormonal therapy alone, and 4 received chemotherapy alone. One patient received surgical treatment alone, and 1 patient remained untreated. A complete remission was achieved in 35 patients (83%), but a second supraclavicular recurrence occurred in 12 (34% of patients who achieved complete remission). There were 6 patients (14%) who were alive, without evidence of disease, after a follow-up period of 4.4 to 8.3 years. Nonetheless, the 5-year overall survival and distant disease survival rates based on the date of diagnosis of supraclavicular recurrence were 38% (95% CI, 23%-53%) and 22% (95% CI, 8%-35%), respectively. The distant disease-free survival rate was somewhat better for the 25 patients who underwent radiotherapy as part of the treatment for supraclavicular recurrence than it was for the 17 patients who did not receive radiotherapy (P = .06). When the 8 patients who had received axillary and supraclavicular radiotherapy as part of their initial treatment were excluded, the difference became more dramatic (P = .002). Thus, the experience from this community setting indicates that isolated supraclavicular recurrence occurs uncommonly, but when it does, it is an indicator of soon-to-develop distant metastases. The overall local control rate was quite high with radiotherapy.

Comment by William B. Ershler, MD

It is now established that the appearance of supraclavicular nodes is a poor prognostic factor in breast cancer.1 A recent report from M.D. Anderson2 examining the treatment of 70 patients with solitary ipsilateral supraclavicular metastases at first presentation resulted in the argument for developing a treatment strategy specific for this distribution of disease. Brito and colleagues advocated the inclusion of supraclavicular disease in stage III (rather than in stage IV). Ultimately, this recommendation has been followed by the International Union Against Cancer in the most recent edition of the TNM Classification of Malignant Tumors.3 Now, patients with metastases in the supraclavicular lymph nodes are classified as N3c/pN3c and a new stage, stage III C that includes N3 (pN3a, pN3b, pN3c) M0 has been introduced. Previously these malignancies had been classified as M1, and accordingly, Stage IV.

It is logical to think that patients with isolated recurrence in supraclavicular nodes also fall into an intermediate category with regard to prognosis. The data in this report from The Netherlands indicate that local control can be achieved by radiation therapy, but the numbers were too small to demonstrate any survival advantage by additional chemotherapy. Chemotherapy or hormonal therapy alone was less likely to produce local control. Based upon this review, it would seem reasonable that optimal therapy for patients with isolated supraclavicular nodes would include a multimodality approach using local radiotherapy in association with systemic therapy (hormonal or chemotherapy). It remains to be demonstrated that such an approach would result in improved survival (when compared to local therapy alone), but short of a clinical trial established in this particular setting (and unlikely to happen anytime soon), extrapolation from the experience in the adjuvant setting after definitive surgery or radiation therapy would seem reasonable.

References

1. DeBois JM. Strahlenther Onkol. 1997;173:1-12.

2. Brito RA, et al. J Clin Oncol. 2001;19:628-633.

3. Sobin LH, et al, eds. TNM Classification of Malignant Tumors, 6th edition. New York, NY: John Wiley & Sons. 2002:131-141.

Dr. Ershler is UNOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, D.C.