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Cellular and Molecular Biology

Comment on “The lingering mysteries of metastatic recurrence in breast cancer”

British Journal of Cancer volume 128, pages 484–485 (2023)Cite this article

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We have read with interest the excellent commentary on “The lingering mysteries of metastatic recurrence in breast cancer” [1]. The article carefully and thoroughly reviews many explanations for metastatic recurrence. However, the primary emphasis is on what we would refer to as cancer cell-intrinsic pathways. By this, we mean that the article has, as its primary focus, alterations that are primarily restricted to the breast cancer cells themselves, which either contribute to their metastatic potential or their ability to overcome so-called dormancy. While these explanations are unquestionably important, we believe they fail to fully recognise critical non-tumour cell intrinsic (tumour microenvironment) or non-tumour extrinsic (host) aspects of the control of metastatic recurrence in women with breast cancer.

Firstly, it is critical to recognise several remarkable features of breast cancer recurrence, particularly of the oestrogen receptor-positive (ER+) subtypes. While oestrogen receptor-negative (ER−) breast cancers initially tend to have an earlier likelihood of recurrence, eventually, ER+ breast cancers catch up. In fact, multiple studies have shown that even following 5 years of disease-free survival and optimal administration of prophylactic adjuvant endocrine therapy, the recurrence of ER+ breast cancer is essentially a straight line for the next 25 years [2]. This implies that, if it were not for other inevitable causes of mortality, ER+ breast cancer would essentially be incurable. Multiple studies have shown that circulating breast cancer cells present many years following apparently curative therapy [3]. Studies of bone marrow sampling show that, even within 5 mL of sampled marrow, 30–40% of women can be shown to have viable breast cancer cells [4]. While this is a negative prognostic variable, within the timeframe of 5–10 years, many women with positive marrows still have not recurred. Clearly, this persistent appearance of metastatic disease over time must be considered in any analysis of drivers of metastasis.

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  1. Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Washington, DC, USA

    Barry I. Hudson & Marc E. Lippman

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  1. Barry I. Hudson
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BIH drafted and edited the manuscript. MEL drafted and edited the manuscript.

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Correspondence to Barry I. Hudson.

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Hudson, B.I., Lippman, M.E. Comment on “The lingering mysteries of metastatic recurrence in breast cancer”. Br J Cancer 128, 484–485 (2023). https://doi.org/10.1038/s41416-022-02012-0

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