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. 2014 Aug;146(3):627-36.
doi: 10.1007/s10549-014-3057-9. Epub 2014 Jul 20.

Differences in metastatic patterns in relation to time between primary surgery and first relapse from breast cancer suggest synchronized growth of dormant micrometastases

Hanna Dillekås  1 , Monica Transeth, Martin Pilskog, Jörg Assmus, Oddbjørn Straume
Affiliations

Differences in metastatic patterns in relation to time between primary surgery and first relapse from breast cancer suggest synchronized growth of dormant micrometastases

Hanna Dillekås et al. Breast Cancer Res Treat. 2014 Aug.

Abstract

A significant variation in the metastatic pattern among breast cancer patients exists. Clinical observations suggest that these differences are related to time to recurrence (TTR), thus suggesting a common systemic growth signal at the time of surgery. Our goal was to identify a marker for synchronized growth of micrometastases. To quantify the metastatic pattern at first relapse, 180 patients with metastatic breast cancer were studied. Standard deviation (SD) of lesions size and lesion number was calculated and served as a marker for variation. Patients with low SD (multiple/similar sized lesions) were assumed to have synchronized growth, whereas patients with high SD were assumed to have unsynchronized growth. Patients were grouped according to TTR; early (< 3 years-) or late (> 3 years- after surgery). In patients not receiving systemic adjuvant treatment, median SD was significantly lower in the early group (2.5 mm) compared with 6.4 mm in the late group (p = 0.005). In node negative patients, median SD was significantly lower in the early group (3.0 mm) when compared with the late group (5.7 mm, p = 0.02). An additional drop in SD was observed immediately after end of adjuvant endocrine therapy. Our results identify SD as a marker of synchronized metastatic growth in breast cancer. A metastatic phenotype characterized by multiple similar sized metastases, suggesting synchronized onset of growth of micrometastases was predominantly found in patients recurring early after surgery and was counteracted by adjuvant treatment. Systemic growth signals caused by surgery might be antagonized during the time window following surgery.

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Figures

Fig. 1
Fig. 1
Patient with multiple similar sized metastases at the time of first recurrence and with low standard deviation (SD) of size and number of metastatic lesions (a). Patient with one large liver metastasis (red line) and two small metastases lung metastases at the time of the first recurrence (only one is shown here, red arrow) and with high SD (b, c)
Fig. 2
Fig. 2
Annual recurrence hazard rate (± SE) in 180 patients recorded with metastatic breast cancer at Haukeland university Hospital during 2005–2009
Fig. 3
Fig. 3
Metastatic pattern in 180 breast cancer patients. The plots show the mean of the standard deviation (SD) of size and number of metastases in each patient at first recurrence (± SE) according to time after surgery. a All cases. b Box plot of mean SD according to early recurrences (0–3 years) versus late recurrences (3 + years), all cases. c, d Node negative cases e, f Cases with no systemic adjuvant treatment. *Mann–Whitney test
Fig. 4
Fig. 4
Metastatic pattern in the subgroup of breast cancer patients treated with adjuvant endocrine therapy. a Mean of the standard deviation (SD) of size and number of metastases in each patient at first recurrence (± SE) according to time after surgery. b Box plot of mean SD compared between the time before versus after cessation of adjuvant endocrine treatment. *Mann–Whitney test
See this image and copyright information in PMC

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