Are 90% of deaths from cancer caused by metastases?

Numerous publications have stated that metastases are responsible for 90% of cancer deaths, but data underlying this assertion has been lacking. Our objective was to determine what proportions of cancer deaths are caused by metastases. Population-based data from the Cancer Registry of Norway for the years 2005-2015 was analyzed. We compared all deaths in the Norwegian population where a cancer diagnosis was registered as cause of death. Deaths caused by cancer, with and without metastases, were analyzed, by sex and tumor group. For solid tumors, 66.7% of cancer deaths were registered with metastases as a contributing cause. Proportions varied substantially between tumor groups. Our data support the idea that the majority of deaths from solid tumors are caused by metastases. Thus, a better understanding of the biology of metastases and identification of druggable targets involved in growth at the metastatic site is a promising strategy to reduce cancer mortality.

Distant metastasis dynamics following subsequent surgeries after primary breast cancer removal.

BACKGROUND: The aim of the research was to separate the distant metastasis (DM) enhancing effect due to breast tumour removal from that due to surgical manoeuvre by itself. METHODS: DM dynamics following surgery for ipsilateral breast tumour recurrence (IBTR), contralateral breast cancer (CBC) and delayed reconstruction (REC), which was performed after the original breast cancer surgical removal, was analysed. A total of 338 patients with IBTR, 239 with CBC and 312 with REC were studied. RESULTS: The DM dynamics following IBTR, CBC and REC, when assessed with time origin at their surgical treatment, is similar to the analogous pattern following primary tumour removal, with a first major peak at about 18 months and a second lower one at about 5 years from surgery. The time span between primary tumour removal and the second surgery is influential on DM risk levels for IBTR and CBC patients, not for REC patients. CONCLUSIONS: The role of breast tumour removal is different from the role of surgery by itself. Our findings suggest that the major effect of reconstructive surgery is microscopic metastasis acceleration, while breast tumour surgical removal (either primary or IBTR or CBC) involves both tumour homeostasis interruption and microscopic metastasis growth acceleration. The removal of a breast tumour would eliminate its homeostatic restrains on metastatic foci, thus allowing metastasis development, which, in turn, would be supported by the forwarding action of the mechanisms triggered by the surgical wounding.

The link between wound healing and escape from tumor dormancy.

Tumor dormancy is considered one of the major unsolved questions in cancer biology. Understanding the mechanisms responsible for maintaining and interrupting dormancy would be a major step towards preventing overt metastatic disease. Increasing evidence points to tissue trauma and subsequent wound healing as contributing events in escape from dormancy. In this review, we outline relevant aspects of the wound healing process, and relate this to mechanisms of tumor dormancy and metastatic progression. In addition to important findings in epidemiological and experimental studies, more direct evidence of such a link has recently been presented. These results can have major implications for treatment and prevention of cancer.

The recurrence pattern following delayed breast reconstruction after mastectomy for breast cancer suggests a systemic effect of surgery on occult dormant micrometastases.

The purpose of this study was to characterize the recurrence dynamics in breast cancer patients after delayed reconstruction. We hypothesized that surgical reconstruction might stimulate dormant micrometastases and reduce time to recurrence. All mastectomy breast cancer patients with delayed surgical reconstruction at Haukeland University Hospital, between 1977 and 2007, n = 312, were studied. Our control group consisted of 1341 breast cancer patients without reconstruction. For each case, all patients in the control group with identical T and N stages and age ±2 years were considered. A paired control was randomly selected from this group. 10 years after primary surgery, 39 of the cases had relapsed, compared to 52 of the matched controls. The reconstructed group was analyzed for relapse dynamics after mastectomy; the first peak in relapses was similarly timed, but smaller than for the controls, while the second peak was similar in time and size. Second, the relapse pattern was analyzed with reconstruction as the starting point. A peak in recurrences was found after 18 months, and a lower peak at the 5th-6th year. The height of the peak correlated with the extent of surgery and initial T and N stages. Timing of the peak was not affected, neither was the cumulative effect. The relapse pattern, when time origin is placed both at mastectomy and at reconstruction, is bimodal with a peak position at the same time points, at 2 years and at 5-6 years. The timing of the transition from dormant micrometastases into clinically detectable macrometastases might be explained by an enhancing effect of surgery.

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

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.