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An unusual case of breast cancer relapse after 30 years of disease-free survival.


There are few reported cases of recurrence decades after disease-free survival following loco-regional treatment of breast cancer. Here, we report a case of a woman treated with mastectomy and radiotherapy in 1965, who presented with a pleural mass and high CA15.3 concentrations in a pleural effusion 30 years later and who responded to endocrine therapy.

Case history

A 77-year-old woman was referred to the Geriatric Department of Ospedale Maggiore, Milan in June 1995 with mild dyspnoea of recent onset. Her background history included right-sided breast cancer treated with mastectomy and radiotherapy at the age of 47 without specific follow-up, hysterectomy and oophorectomy at the age of 48, and pulmonary tuberculosis at the age of 42. Intercurrent problems were hypertension with recurrent transient ischaemic attacks, surgery for abdominal aortic aneurysm at the age of 73 and recent peptic ulcer which had responded to H2 antagonists.

Physical examination was negative apart from dullness at the fight lung base with decreased vocal fremitus and diminished breath sounds.

Routine biochemistry and haematology was normal, including inflammatory markers.

Chest X-ray revealed right basal opacification. A chest computed tomography (CT) scan showed a solid mass 4 cm in diameter at the right costa-vertebral angle with an ipsi-lateral pleural effusion, without enlargement of mediastinal lymph nodes.

The pleural aspirate was bloody and the cytological examination positive for adenocarcinomatous cells. Cancer was confirmed by cytological examination of the aspirated thoracic mass. It was not possible to define the status of oestrogen receptors. Further examinations (bone scan, left mammography, abdominal and thyroid ultra sound, brain CT) excluded multiorgan involvement. High concentrations of CA 15.3 were detected in the pleural effusion (1062 U/ml) but not in the serum sample (46.04 U/ml). Carcinoembryonic antigen and CA 19.9 were within normal ranges in both serum and pleural fluid.

The history, the cytological examination and the high concentration of CA 15.3 suggested the diagnosis of possible metastatic breast cancer. We prescribed endocrine therapy with 20mg/day tamoxifen. Local treatment was considered unnecessary in the absence of important respiratory symptoms after thoracentesis [2].

Chest CTs 3 and 11 months later showed progressive reduction of the costa-vertebral mass and complete regression of the pleural effusion, associated with the decline in circulating CA 15.3 concentrations. Two years after starting endocrine treatment, the response has been maintained.


This case is an example of prolonged disease-free survival after loco-regional therapy for breast cancer. There are few reported cases of relapse after 20 years. The patient did not report any clinical features of disease during the 30 years after surgery and radiotherapy. We have assumed that this long period as a disease-free interval corroborates the `tumour dormancy' hypothesis [3]. The factors involved in switching from `dormant' phenotype to clinical relapse are uncertain, but a disequilibrium between circulating angiogenesis factors and their inhibitors has been hypothesized. Recent studies have revealed the role of hormonal factors on disease-free interval, showing that oestrogens stimulate the growth of micro-metastases in pre-menopausal women with breast cancer, but it is not clear if disease-free interval in post-menopausal patients depends on plasma oestrogen concentrations [4]. However, a positive relationship between hormone receptors and prolonged disease-free interval has been described [5]. In our case, the clinical response to tamoxifen supports this relationship, although the patient's receptor status was unknown. We consider the response to hormonal therapy proof of the breast origin of the pleural lesion.

An additional issue in this case is the value of the CA 15.3 assay in serosal fluids. In our patient, high CA 15.3 concentrations in the pleural effusion were associated with normal serum concentrations. In follow-up studies, serum CA 15.3 is useful, offering a sensitivity of 82.8% and a specificity of 95.7% [6, 7]. Its estimation in effusions is not routinely recommended [8], but in our case it helped treatment decisions.

Key points

* Patients who have had breast cancer treated even 30 years ago may present with local or distant recurrence.

* If the origin of a cancer is undefined, the concentration of the tumour marker CA 15.3 in serosal effusions can be diagnostically useful.


[1.] Hayes DF. Tumor markers for breast cancer. Current utilities and future prospects. Hematol Oncol Clin North Am 1994; 3: 485-501.

[2.] Perrone F, Carlomagno C, De Placido S, Lauria R, Morabito A, Bianco AR. First-line systemic therapy for metastatic breast cancer and management of pleural effusion. Ann Oncol 1995; 6: 1033-43.

[3.] Demicheli R, Abbattista A, Miceli R, Valagussa P, Bonadonna G. Time distribution of the recurrence risk for breast cancer patients undergoing mastectomy: further support about the concept of tumor dormancy. Breast Cancer Res Treat 1996; 41: 177-85.

[4.] Lonning PE, Helle SI, Johannessen DC, Ekse D, Adlercreutz H. Influence of plasma oestrogen levels on the length of the disease-free interval in postmenopausal women with breast cancer. Breast Cancer Res Treat 1996; 37: 209-16.

[5.] Basso-Ricci S, Coradini D, Bartoli C, Soncini F, Gandola L. Long-term relapses in breast cancer patients (oestrogen receptor status). Tumori 1995; 81: 265- 7.

[6.] Hou MF, Huang TJ, Hsieh JS et al. Comparison of serum CA 15.3 and CEA in breast cancer. Kao Hsiung I Hsueh Ko Hsueh Tsa Chih 1995; 11: 660-6.

[7.] Vizcarra E, Lluch A, Cibrian R et al. Value of CA 15.3 in breast cancer and comparison with CEA and TPA: a study of specificity in disease free follow up patients and sensitivity in patients at diagnosis of the first metastasis. Breast Cancer Res Treat 1996; 37: 209-16.

[8.] Pinto MM. CA 15.3 assay in effusions: comparison with carcino-embryonic antigen and CA 125 assay and cytologic diagnosis. Acta Cytol 1996; 40: 437-42.

Received 3 April 1998; accepted 14 April 1998


Dipartimento di Medicina Interna, Cattedra di Gerontologia e Geriatria, Universita' di Milano e Ospedale Maggiore, IRCCS-Milano, via Pace 9, 20122 Milan, Italy

Address correspondence to: G. Annoni. Fax: (+39) 2 5464615. E-mail:
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Publication:Age and Ageing
Date:Sep 1, 1998
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