Does surgery unfavourably perturb the “natural history” of early breast cancer by accelerating the appearance of distant metastases?

Baum, Michael; Demicheli, Romano; Hrushesky, William J. M.; Retsky, Michael

doi:10.1016/j.ejca.2004.09.031

Cited by 172 publications

(115 citation statements)

References 35 publications

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“…Opposite to the proposed biological mechanisms in favor of surgical removal of the primary tumor, there have been observations indicating that surgical resection of the breast lesion in metastatic disease may accelerate relapse by two mechanisms: 1. due to removal of inhibitors of angiogenesis there will be an angiogenic surge; 2. surgical wounding will lead to the release of growth and immunosuppressive factors [10,31]. Some other studies also suggest that the growth of distant metastases even may be stimulated after the primary breast tumor has been removed; this hypothesis is partly sustained by experimental studies and partly by doctor's personal experience [32]. Our analysis of available retrospective studies does not support this view.…”

Section: Total (95% Ci)mentioning

confidence: 64%

Impact of breast surgery on survival in patients with distant metastases at initial presentation: a systematic review of the literature

Ruiterkamp

Voogd

Bosscha

et al. 2009

Breast Cancer Res Treat

103

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According to current treatment standards, patients with metastatic breast cancer at diagnosis receive palliative therapy. Local treatment of the breast is only recommended if the primary tumor is symptomatic. Recent studies suggest that surgical removal of the primary tumor has a favorable impact on the prognosis of patients with primary metastatic breast cancer. We performed a systematic review of the literature to weigh the evidence for and against breast surgery in this patient group. Ten retrospective studies were found in which the use of breast surgery in primary metastatic breast cancer and its impact on survival was examined. The hazard ratios of the studies were pooled to provide an estimate of the overall effect of surgery, and the results and conclusions of the studies were analyzed. A crude analysis, without adjustment for potential confounders, showed that surgical removal of the breast lesion in stage-IV disease was associated with a significantly higher overall survival rate in seven of the ten studies, and a trend toward a better survival in the three remaining studies. Surgery of the primary tumor appeared to be an independent factor for an improved survival in the multivariate analyses from the individual studies, with hazard ratios ranging from 0.47 to 0.71. The pooled hazard ratio for overall mortality was 0.65 (95% CI 0.59-0.72) in favor of the patients undergoing surgery. This systematic review of the literature suggests that surgery of the primary breast tumor in patients with stage-IV disease at initial presentation does have a positive impact on survival. In order to provide a definite answer on whether local tumor control in patients with primary metastatic disease improves survival, a randomized controlled trial comparing systemic therapy with and without breast surgery is needed.

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Section: Total (95% Ci)mentioning

confidence: 64%

Impact of breast surgery on survival in patients with distant metastases at initial presentation: a systematic review of the literature

Ruiterkamp

Voogd

Bosscha

et al. 2009

Breast Cancer Res Treat

103

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“…Therefore, early genetic divergence of metastases favors a parallel model (16) in which frequently disseminated cancer cells rarely establish themselves, rather than a linear model (13) of cancer evolution requiring somatic mutations to produce metastases. The observed early genetic divergence of metastases has implications for the retrospective examination of medical care, including whether surgery is seeding distant metastases (17). For example, claims that metastases necessarily arose subsequent to a delay in diagnosis and resection could be refuted.…”

Section: Inference Of Cancer Chronograms Revealed the Early Genetic Dmentioning

confidence: 99%

Early and multiple origins of metastatic lineages within primary tumors

Zhao

Bai

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

143

133

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Many aspects of the evolutionary process of tumorigenesis that are fundamental to cancer biology and targeted treatment have been challenging to reveal, such as the divergence times and genetic clonality of metastatic lineages. To address these challenges, we performed tumor phylogenetics using molecular evolutionary models, reconstructed ancestral states of somatic mutations, and inferred cancer chronograms to yield three conclusions. First, in contrast to a linear model of cancer progression, metastases can originate from divergent lineages within primary tumors. Evolved genetic changes in cancer lineages likely affect only the proclivity toward metastasis. Single genetic changes are unlikely to be necessary or sufficient for metastasis. Second, metastatic lineages can arise early in tumor development, sometimes long before diagnosis. The early genetic divergence of some metastatic lineages directs attention toward research on driver genes that are mutated early in cancer evolution. Last, the temporal order of occurrence of driver mutations can be inferred from phylogenetic analysis of cancer chronograms, guiding development of targeted therapeutics effective against primary tumors and metastases.tumor phylogenetics | ancestral reconstruction | cancer | chronograms | oncogenes I t has long been understood that tumorigenesis is an evolutionary process (1) associated with the accumulation of somatic mutations (2). However, many aspects of that process that are fundamental to cancer biology and targeted treatment have been challenging to reveal, such as the divergence times and genetic clonality of metastatic lineages (3, 4). Somatic mutations have revealed tumor type-specific drivers by comparison of primary tumor and normal tissues (5, 6), and studies examining the evolutionary process of cancer across multiple sites have used a handful of subjects to identify ubiquitous, shared, and private mutations (1) and to reconstruct a number of tumor phylogenies using parsimony or unweighted pair group methods with arithmetic mean (1, 7) but have lacked the power to generalize about the tumorigenic or metastatic process across cancer types (1).Tumor phylogenetics, using a larger sample with explicit evolutionary models, can be applied using molecular evolutionary models to reconstruct ancestral states of somatic mutations and infer cancer chronograms, revealing novel information about the timing of gene mutations and their contributions to tumorigenesis and metastasis and addressing three fundamental aspects of cancer biology. First, the topology of divergence of primary and metastatic lineages can differentiate between a linear model of cancer progression, in which all metastatic tumors are descended from a single original primary cell such that all metastases are more closely related to each other than they are to any tissue in the primary tumor, and a branched model, in which metastases can originate from divergent lineages within primary tumors. Second, molecular evolutionary trees and chronograms can quantify how e...

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“…Удаление первичной опухоли таким больным обычно не рекомендуется. Более того, распространено мнение, что такой подход может даже стимулировать прогрессирование заболе-вания [9][10][11][12][13]. Безусловными показаниями к удалению первичной опухоли при наличии отдаленных мета-стазов являются местные осложнения заболевания -кровотечение, распад опухоли.…”

Section: опухоли женской репродуктивной системы Tumors Of Female Reprunclassified

Evaluation of the scientific results of the study entitled “Opportunities for surgical treatment of patients with stage IV breast cancer” performed by Russian Society of Oncomammologists (RSOM)

Bozhok¹,

Топузов²,

Зикиряходжаев³

et al. 2016

Tumors of female reproductive system

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ОПУХОЛИ ЖЕНСКОЙ РЕПРОДУКТИВНОЙ СИСТЕМЫ TUMORS OF FEMALE REPRODUCTIVE SYSTEM Russia; 3 2nd Botkinskiy Proezd, Moscow 125284, Russia; 5 N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia; 23 Kashirskoe Shosse, Moscow 115478, Russia; 6 Rostov Research Institute of Oncology, Ministry of Health of Russia; 63 14th Liniya St., Rostov-on-Don 344037, Russia; 7 N.N. Petrov Research Institute of Oncology, Ministry of Health of Russia; 68, Leningradskaya St., Pesochnyi Settlement, Saint Petersburg 197758, Russia

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Does surgery unfavourably perturb the “natural history” of early breast cancer by accelerating the appearance of distant metastases?

Cited by 172 publications

References 35 publications

Impact of breast surgery on survival in patients with distant metastases at initial presentation: a systematic review of the literature

Impact of breast surgery on survival in patients with distant metastases at initial presentation: a systematic review of the literature

Early and multiple origins of metastatic lineages within primary tumors

Evaluation of the scientific results of the study entitled “Opportunities for surgical treatment of patients with stage IV breast cancer” performed by Russian Society of Oncomammologists (RSOM)

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