Elsevier

European Journal of Cancer

Volume 47, Issue 14, September 2011, Pages 2099-2106
European Journal of Cancer

The role of ipsilateral breast radiotherapy in management of occult primary breast cancer presenting as axillary lymphadenopathy

https://doi.org/10.1016/j.ejca.2011.05.010Get rights and content

Abstract

Aim

To assess the role of ipsilateral breast radiotherapy (IBR) in women with occult primary breast cancer presenting with axillary metastases (OPBC).

Methods

Patients with axillary nodal metastases and histological diagnosis of breast cancer without palpable, mammographic or ultrasonographic evidence of a breast primary were identified from a prospectively maintained single institution database. Imaging, surgery, radiotherapy, recurrence and survival data were collected. Patients whose breast cancer primary was detected on MRI (but occult on clinical examination and other imaging) were excluded from the analyses of IBR and outcome, but were included in other exploratory analyses.

Results

Fifty-five patients were included between 1975 and 2009. Median follow up was 68 months. Twenty patients had breast magnetic resonance imaging (MRI) in addition to other imaging. A primary breast cancer was detected in 7 of these 20. 48/55 patients had no detectable breast primary. 35/48 patients (73%) were treated with radiotherapy to the conserved breast, and 13/48 (27%) with observation. Patients who had IBR had better 5 year local recurrence free survival (LRFS) (84% versus 34%, p < 0.001), and relapse free survival (RFS) (64% versus 34%, p = 0.05), but no difference in overall survival (OS) (84% versus 85%, p = 0.2). There was no difference in 5 year LRFS (80% versus 90%: p = 0.3) between patients who received radiation of 50 Gy in 25 fractions versus ⩾60 Gy.

Conclusion

Patients with OPBC should be managed with IBR and breast conservation, or mastectomy. Our data suggest it is not necessary to irradiate the breast to more than 50 Gy in 25 fractions.

Introduction

Breast cancer presenting as axillary adenopathy with clinically occult breast tumour was first described by Halsted in 1907.1 Reported series suggest that 0.3–1% of early breast cancers present with axillary metastases in the absence of a breast primary on clinical examination or mammography.2, 3, 4 Where mastectomy is performed in such patients, a primary breast cancer is found in 45–82% patients.3, 5, 6, 7, 8, 9 However, where the breast primary is occult following breast MRI in addition to clinical examination, mammogram and ultrasound, the frequency of detection of breast primary in mastectomy specimen is lower (20–33%).10, 11 Where the ipsilateral breast is untreated following removal of involved axillary lymph nodes, clinical ipsilateral breast cancer develops in around 40% of patients,7, 12, 13, 14, 15 such that many guidelines and authors recommend local treatment of the ipsilateral breast in OPBC.16, 17 However, not all guidelines are in concordance with this advice, with European guidelines published in 2003 recommending against radiotherapy and surgery when breast MRI is negative.18

Traditionally, in the setting of OPBC, the ipsilateral breast was treated with mastectomy. However, small retrospective series comparing mastectomy to breast irradiation reported no difference in local control or survival.3, 12, 19, 20 Given the cosmetic advantage of breast conservation, IBR has become the treatment of choice.19, 20, 21, 22, 23

Retrospective series infrequently describe breast radiotherapy dose and fractionation. One series19 reported use of an escalated dose schedule of 60 Gy in 30 fractions whilst two others reported use of a standard adjuvant dose of 50 Gy in 25 fractions.12, 20, 24 However, to our knowledge no series has compared outcome in patients treated using different dose and fractionation schedules.

In the past decade breast MRI has come into routine practise, and is now recommended where patients present with axillary metastases from an occult primary breast cancer.12, 16, 25, 26, 27 MRI has high sensitivity in detecting occult primary tumours in the breast, and may facilitate breast-conserving surgery.10, 11, 12, 27, 28, 29, 30, 31

This study updates a previously published series of 29 patients from the Royal Marsden Hospital,21 with the aim of confirming, in a larger series, that treating occult primary breast cancer with IBR is a safe alternative to mastectomy in terms of local control and survival. We add to the literature a comparison of outcomes in patients treated using two different IBR dose and fractionation schedules, a comparison of local therapy versus no treatment, and an assessment of whether or not the incorporation of breast MRI into investigations helps reduce loco-regional recurrence.

Section snippets

Study population

Patients with axillary lymph node metastases and histological diagnosis compatible with a breast cancer primary without palpable, mammographic or ultrasonographic evidence of a primary breast cancer were identified from a prospectively maintained single institution data base (Royal Marsden Hospital, London, UK) between 1975 and 2009. Patients with metastatic or advanced loco-regional (Stage IIIC) disease, primary breast cancer incidentally detected on staging CT imaging, previous breast cancer,

Patient characteristics

Seventy-two patients were identified between 1975 and 2009, including 29 patients from the previously reported series.21 Seventeen patients were excluded for the following reasons: history of contralateral breast cancer (4), subsequent breast primary identified (1), non-breast histological diagnosis on review (1), incomplete data (1), breast primary arising in ectopic tissue (1), advanced breast cancer at diagnosis (7), and breast primary detected on staging CT (2). Therefore, 55 patients were

Discussion

The previously published series from our institution found that, in patients who presented with axillary lymphadenopathy from OPBC, breast conservation is a feasible alternative to mastectomy, but recommended that the ipsilateral breast be treated with radiotherapy to reduce local recurrence.21 These updated results provide further support for this recommendation by showing that IBR significantly improves LRFS and RFS compared to breast observation.

Limitations of our study include its

Conclusion

Patients who have occult primary breast cancer with axillary metastases should be managed with local treatment of the ipsilateral breast. Where the ipsilateral breast is conserved, IBR is recommended to improve local control. No difference in outcome was found between patients treated with a standard breast radiotherapy fractionation and schedule (50 Gy/25 fractions or 40 Gy /15 fractions) and those treated 60 Gy/30 fractions.

Conflict of interest statement

None declared.

Acknowledgements

Sarah Barton would like to thank the Cridlan Fund for funding support. We acknowledge NHS funding to the NIHR Biomedical Research Centre.

References (36)

  • W.T. Fitts et al.

    Prognosis of occult carcinoma of the breast

    Am J Surg

    (1963)
  • R. Ashikari et al.

    Breast cancer presenting as an axillary mass

    Ann Surg

    (1976)
  • M. Merson et al.

    Breast carcinoma presenting as axillary metastases without evidence of a primary tumor

    Cancer

    (1992)
  • J. Patel et al.

    Axillary lymph node metastasis from an occult breast cancer

    Cancer

    (1981)
  • X. Wang et al.

    Clinical benefits of mastectomy on treatment of occult breast carcinoma presenting axillary metastases

    Breast J

    (2010)
  • C.L. Buchanan et al.

    Utility of breast magnetic resonance imaging in patients with occult primary breast cancer

    Ann Surg Oncol

    (2005)
  • J.A. Olson et al.

    Magnetic resonance imaging facilitates breast conservation for occult breast cancer

    Ann Surg Oncol

    (2000)
  • N. Ellerbroek et al.

    Treatment of patients with isolated axillary nodal metastases from an occult primary carcinoma consistent with breast origin

    Cancer

    (1990)
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