Does breast cancer growth rate really depend on tumor subtype? Measurement of tumor doubling time using serial ultrasonography between diagnosis and surgery



Breast cancer growth is generally expected to differ between tumor subtypes. We aimed to evaluate tumor doubling time (DT) using ultrasonography and verify whether each tumor subtype has a unique DT.


This retrospective study included 265 patients with invasive breast cancer who received serial ultrasonography between diagnosis and surgery. Tumor diameters were measured in three directions and DTs were calculated according to an exponential growth model using the volume change during serial ultrasonography. We investigated the relationships between DT, tumor subtype, and histopathological factors.


Volumes did not change in 95 (36%) of 265 tumors and increased in 170 (64%) tumors during serial ultrasonography (mean interval, 56.9 days). The mean volume increases of all tumors and volume-increased tumors were 22.1% and 34.5%, respectively. Triple-negative tumors had greater volume increases (40% vs. 20%, p = 0.001) and shorter DT (124 vs. 185 days, p = 0.027) than estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– tumors. Volume-increased tumors had higher Ki-67 indices than those of volume-stable tumors in ER+/HER2− (p = 0.002) and ER+/HER2+ tumors (p = 0.011) and higher histological grades in all tumors except triple-negative tumors (p < 0.001). Triple-negative tumors with DTs < 90 days (short-DT) showed higher Ki-67 indices than those with DTs > 90 days (long-DT) (p = 0.008). In ER+/HER2− tumors, histological grades were higher for short-DT than for long-DT tumors (p = 0.022).


Differences in tumor DT depending on breast cancer subtype, Ki-67 index, and histological grade were confirmed using serial ultrasonography even during preoperative short interval.

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We thank Enago ( for the English language review.

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Correspondence to Kazuaki Nakashima.

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Nakashima, K., Uematsu, T., Takahashi, K. et al. Does breast cancer growth rate really depend on tumor subtype? Measurement of tumor doubling time using serial ultrasonography between diagnosis and surgery. Breast Cancer 26, 206–214 (2019).

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  • Breast cancer
  • Ultrasonography
  • Molecular subtype
  • Tumor growth rate
  • Doubling time