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Published in: Breast Cancer 2/2019

01-03-2019 | Original Article

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

Authors: Kazuaki Nakashima, Takayoshi Uematsu, Kaoru Takahashi, Seiichirou Nishimura, Yukiko Tadokoro, Tomomi Hayashi, Takashi Sugino

Published in: Breast Cancer | Issue 2/2019

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Abstract

Background

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.

Methods

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.

Results

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).

Conclusion

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.
Literature
1.
go back to reference Richardson LC, Royalty J, Howe W, Helsel W, Kammerer W, Benard VB. Timeliness of breast cancer diagnosis and initiation of treatment in the National Breast and Cervical Cancer Early Detection Program, 1996–2005. Am J Public Health. 2010;100:1769–76.CrossRefPubMedPubMedCentral Richardson LC, Royalty J, Howe W, Helsel W, Kammerer W, Benard VB. Timeliness of breast cancer diagnosis and initiation of treatment in the National Breast and Cervical Cancer Early Detection Program, 1996–2005. Am J Public Health. 2010;100:1769–76.CrossRefPubMedPubMedCentral
2.
go back to reference Bleicher RJ, Ruth K, Sigurdson ER, Beck JR, Ross E, Wong YN, et al. Time to Surgery and Breast Cancer Survival in the United States. JAMA Oncol. 2016;2:330–9.CrossRefPubMedPubMedCentral Bleicher RJ, Ruth K, Sigurdson ER, Beck JR, Ross E, Wong YN, et al. Time to Surgery and Breast Cancer Survival in the United States. JAMA Oncol. 2016;2:330–9.CrossRefPubMedPubMedCentral
3.
go back to reference Neal RD, Tharmanathan P, France B, Din NU, Cotton S, Fallon-Ferguson J, et al. Is increased time to diagnosis and treatment in symptomatic cancer associated with poorer outcomes? Systematic review. Br J Cancer. 2015;112(Suppl 1):92–107.CrossRef Neal RD, Tharmanathan P, France B, Din NU, Cotton S, Fallon-Ferguson J, et al. Is increased time to diagnosis and treatment in symptomatic cancer associated with poorer outcomes? Systematic review. Br J Cancer. 2015;112(Suppl 1):92–107.CrossRef
4.
go back to reference Friberg S, Mattson S. On the growth rates of human malignant tumors: implications for medical decision making. J Surg Oncol. 1997;65:284–97.CrossRefPubMed Friberg S, Mattson S. On the growth rates of human malignant tumors: implications for medical decision making. J Surg Oncol. 1997;65:284–97.CrossRefPubMed
5.
6.
go back to reference Kusama S, Spratt JS Jr, Donegan WL, Watson FR, Cunningham C. The gross rates of growth of human mammary carcinoma. Cancer. 1972;30:594–9.CrossRefPubMed Kusama S, Spratt JS Jr, Donegan WL, Watson FR, Cunningham C. The gross rates of growth of human mammary carcinoma. Cancer. 1972;30:594–9.CrossRefPubMed
7.
go back to reference Spratt JS, Greenberg RA, Heuser LS. Geometry, growth rates, and duration of cancer and carcinoma in situ of the breast before detection by screening. Cancer Res. 1986;46:970–4.PubMed Spratt JS, Greenberg RA, Heuser LS. Geometry, growth rates, and duration of cancer and carcinoma in situ of the breast before detection by screening. Cancer Res. 1986;46:970–4.PubMed
8.
go back to reference Weedon-Fekjaer H, Lindqvist BH, Vatten LJ, Aalen OO, Tretli S. Breast cancer tumor growth estimated through mammography screening data. Breast Cancer Res. 2008;10:R41.CrossRefPubMedPubMedCentral Weedon-Fekjaer H, Lindqvist BH, Vatten LJ, Aalen OO, Tretli S. Breast cancer tumor growth estimated through mammography screening data. Breast Cancer Res. 2008;10:R41.CrossRefPubMedPubMedCentral
9.
go back to reference Ho JM, Jafferjee N, Covarrubias GM, Ghesani M, Handler B. Dense breasts: a review of reporting legislation and available supplemental screening options. AJR Am J Roentgenol. 2014;203:449–56.CrossRefPubMed Ho JM, Jafferjee N, Covarrubias GM, Ghesani M, Handler B. Dense breasts: a review of reporting legislation and available supplemental screening options. AJR Am J Roentgenol. 2014;203:449–56.CrossRefPubMed
10.
go back to reference Bosch AM, Kessels AG, Beets GL, Rupa JD, Koster D, van Engelshoven JM, et al. Preoperative estimation of the pathological breast tumour size by physical examination, mammography and ultrasound: a prospective study on 105 invasive tumours. Eur J Radiol. 2003;48:285–92.CrossRefPubMed Bosch AM, Kessels AG, Beets GL, Rupa JD, Koster D, van Engelshoven JM, et al. Preoperative estimation of the pathological breast tumour size by physical examination, mammography and ultrasound: a prospective study on 105 invasive tumours. Eur J Radiol. 2003;48:285–92.CrossRefPubMed
11.
go back to reference Fasching PA, Heusinger K, Loehberg CR, Wenkel E, Lux MP, Schrauder M, et al. Influence of mammographic density on the diagnostic accuracy of tumor size assessment and association with breast cancer tumor characteristics. Eur J Radiol. 2006;60:398–404.CrossRefPubMed Fasching PA, Heusinger K, Loehberg CR, Wenkel E, Lux MP, Schrauder M, et al. Influence of mammographic density on the diagnostic accuracy of tumor size assessment and association with breast cancer tumor characteristics. Eur J Radiol. 2006;60:398–404.CrossRefPubMed
12.
go back to reference Yoo TK, Min JW, Kim MK, Lee E, Kim J, Lee HB, et al. In vivo tumor growth rate measured by US in preoperative period and long term disease outcome in breast cancer patients. PLoS One. 2015;10:e0144144.CrossRefPubMedPubMedCentral Yoo TK, Min JW, Kim MK, Lee E, Kim J, Lee HB, et al. In vivo tumor growth rate measured by US in preoperative period and long term disease outcome in breast cancer patients. PLoS One. 2015;10:e0144144.CrossRefPubMedPubMedCentral
13.
go back to reference Lee SH, Kim YS, Han W, Ryu HS, Chang JM, Cho N, et al. Tumor growth rate of invasive breast cancers during wait times for surgery assessed by ultrasonography. Medicine (Baltimore). 2016;95:e4874.CrossRef Lee SH, Kim YS, Han W, Ryu HS, Chang JM, Cho N, et al. Tumor growth rate of invasive breast cancers during wait times for surgery assessed by ultrasonography. Medicine (Baltimore). 2016;95:e4874.CrossRef
14.
go back to reference Collins VP, Loeffler RK, Tivey H. Observations on growth rates of human tumors. Am J Roentgenol Radium Ther Nucl Med. 1956;76:988–1000.PubMed Collins VP, Loeffler RK, Tivey H. Observations on growth rates of human tumors. Am J Roentgenol Radium Ther Nucl Med. 1956;76:988–1000.PubMed
15.
go back to reference Ryu EB, Chang JM, Seo M, Kim SA, Lim JH, Moon WK. Tumour volume doubling time of molecular breast cancer subtypes assessed by serial breast ultrasound. Eur Radiol. 2014;24:2227–35.CrossRefPubMed Ryu EB, Chang JM, Seo M, Kim SA, Lim JH, Moon WK. Tumour volume doubling time of molecular breast cancer subtypes assessed by serial breast ultrasound. Eur Radiol. 2014;24:2227–35.CrossRefPubMed
16.
go back to reference Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991;19:403–10.CrossRefPubMed Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991;19:403–10.CrossRefPubMed
17.
go back to reference Norton L. A Gompertzian model of human breast cancer growth. Cancer Res. 1988;48:7067–71.PubMed Norton L. A Gompertzian model of human breast cancer growth. Cancer Res. 1988;48:7067–71.PubMed
18.
go back to reference Mehrara E, Forssell-Aronsson E, Ahlman H, Bernhardt P. Specific growth rate versus doubling time for quantitative characterization of tumor growth rate. Cancer Res. 2007;67:3970–5.CrossRefPubMed Mehrara E, Forssell-Aronsson E, Ahlman H, Bernhardt P. Specific growth rate versus doubling time for quantitative characterization of tumor growth rate. Cancer Res. 2007;67:3970–5.CrossRefPubMed
19.
go back to reference von Fournier D, Weber E, Hoeffken W, Bauer M, Kubli F, Barth V. Growth rate of 147 mammary carcinomas. Cancer. 1980;45:2198–207.CrossRef von Fournier D, Weber E, Hoeffken W, Bauer M, Kubli F, Barth V. Growth rate of 147 mammary carcinomas. Cancer. 1980;45:2198–207.CrossRef
20.
go back to reference Peer PG, van Dijck JA, Hendriks JH, Holland R, Verbeek AL. Age-dependent growth rate of primary breast cancer. Cancer. 1993;71:3547–51.CrossRefPubMed Peer PG, van Dijck JA, Hendriks JH, Holland R, Verbeek AL. Age-dependent growth rate of primary breast cancer. Cancer. 1993;71:3547–51.CrossRefPubMed
21.
go back to reference Heuser L, Spratt JS, Polk HC. Jr. Growth rates of primary breast cancers. Cancer. 1979;43:1888–94.CrossRefPubMed Heuser L, Spratt JS, Polk HC. Jr. Growth rates of primary breast cancers. Cancer. 1979;43:1888–94.CrossRefPubMed
22.
go back to reference Dussan C, Zubor P, Fernandez M, Yabar A, Szunyogh N, Visnovsky J. Spontaneous regression of a breast carcinoma: a case report. Gynecol Obstet Invest. 2008;65:206–11.CrossRefPubMed Dussan C, Zubor P, Fernandez M, Yabar A, Szunyogh N, Visnovsky J. Spontaneous regression of a breast carcinoma: a case report. Gynecol Obstet Invest. 2008;65:206–11.CrossRefPubMed
23.
go back to reference Tokunaga E, Okano S, Nakashima Y, Yamashita N, Tanaka K, Akiyoshi S, et al. Spontaneous regression of breast cancer with axillary lymph node metastasis: a case report and review of literature. Int J Clin Exp Pathol. 2014;7:4371–80.PubMedPubMedCentral Tokunaga E, Okano S, Nakashima Y, Yamashita N, Tanaka K, Akiyoshi S, et al. Spontaneous regression of breast cancer with axillary lymph node metastasis: a case report and review of literature. Int J Clin Exp Pathol. 2014;7:4371–80.PubMedPubMedCentral
24.
go back to reference Kuroishi T, Tominaga S, Morimoto T, Tashiro H, Itoh S, Watanabe H, et al. Tumor growth rate and prognosis of breast cancer mainly detected by mass screening. Jpn J Cancer Res. 1990;81:454–62.CrossRefPubMedPubMedCentral Kuroishi T, Tominaga S, Morimoto T, Tashiro H, Itoh S, Watanabe H, et al. Tumor growth rate and prognosis of breast cancer mainly detected by mass screening. Jpn J Cancer Res. 1990;81:454–62.CrossRefPubMedPubMedCentral
25.
go back to reference Tabbane F, Bahi J, Rahal K, el May A, Riahi M, Cammoun M, et al. Inflammatory symptoms in breast cancer. Correlations with growth rate, clinicopathologic variables, and evolution. Cancer. 1989;64:2081–9.CrossRefPubMed Tabbane F, Bahi J, Rahal K, el May A, Riahi M, Cammoun M, et al. Inflammatory symptoms in breast cancer. Correlations with growth rate, clinicopathologic variables, and evolution. Cancer. 1989;64:2081–9.CrossRefPubMed
26.
go back to reference Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011;121:2750–67.CrossRefPubMedPubMedCentral Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011;121:2750–67.CrossRefPubMedPubMedCentral
27.
go back to reference Lehmann BD, Jovanovic B, Chen X, Estrada MV, Johnson KN, Shyr Y, et al. Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection. PLoS One. 2016;11:e0157368.CrossRefPubMedPubMedCentral Lehmann BD, Jovanovic B, Chen X, Estrada MV, Johnson KN, Shyr Y, et al. Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection. PLoS One. 2016;11:e0157368.CrossRefPubMedPubMedCentral
28.
go back to reference Burstein MD, Tsimelzon A, Poage GM, Covington KR, Contreras A, Fuqua SA, et al. Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin Cancer Res. 2015;21:1688–98.CrossRefPubMed Burstein MD, Tsimelzon A, Poage GM, Covington KR, Contreras A, Fuqua SA, et al. Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin Cancer Res. 2015;21:1688–98.CrossRefPubMed
29.
go back to reference Pareja F, Geyer FC, Marchio C, Burke KA, Weigelt B, Reis-Filho JS. Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants. NPJ Breast Cancer. 2016;2:16036.CrossRefPubMedPubMedCentral Pareja F, Geyer FC, Marchio C, Burke KA, Weigelt B, Reis-Filho JS. Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants. NPJ Breast Cancer. 2016;2:16036.CrossRefPubMedPubMedCentral
30.
go back to reference Ono M, Tsuda H, Yunokawa M, Yonemori K, Shimizu C, Tamura K, et al. Prognostic impact of Ki-67 labeling indices with 3 different cutoff values, histological grade, and nuclear grade in hormone-receptor-positive, HER2-negative, node-negative invasive breast cancers. Breast Cancer. 2015;22:141–52.CrossRefPubMed Ono M, Tsuda H, Yunokawa M, Yonemori K, Shimizu C, Tamura K, et al. Prognostic impact of Ki-67 labeling indices with 3 different cutoff values, histological grade, and nuclear grade in hormone-receptor-positive, HER2-negative, node-negative invasive breast cancers. Breast Cancer. 2015;22:141–52.CrossRefPubMed
31.
go back to reference Galante E, Gallus G, Guzzon A, Bono A, Bandieramonte G, Di Pietro S. Growth rate of primary breast cancer and prognosis: observations on a 3- to 7-year follow-up in 180 breast cancers. Br J Cancer. 1986;54:833–6.CrossRefPubMedPubMedCentral Galante E, Gallus G, Guzzon A, Bono A, Bandieramonte G, Di Pietro S. Growth rate of primary breast cancer and prognosis: observations on a 3- to 7-year follow-up in 180 breast cancers. Br J Cancer. 1986;54:833–6.CrossRefPubMedPubMedCentral
32.
go back to reference Heuser LS, Spratt JS, Kuhns JG, Chang AF, Polk HC Jr, Buchanan JB. The association of pathologic and mammographic characteristics of primary human breast cancers with “slow” and “fast” growth rates and with axillary lymph node metastases. Cancer. 1984;53:96–8.CrossRefPubMed Heuser LS, Spratt JS, Kuhns JG, Chang AF, Polk HC Jr, Buchanan JB. The association of pathologic and mammographic characteristics of primary human breast cancers with “slow” and “fast” growth rates and with axillary lymph node metastases. Cancer. 1984;53:96–8.CrossRefPubMed
33.
go back to reference Zhang S, Ding Y, Zhou Q, Wang C, Wu P, Dong J. Correlation Factors Analysis of Breast Cancer Tumor Volume Doubling Time Measured by 3D-Ultrasound. Med Sci Monit. 2017;23:3147–53.CrossRefPubMedPubMedCentral Zhang S, Ding Y, Zhou Q, Wang C, Wu P, Dong J. Correlation Factors Analysis of Breast Cancer Tumor Volume Doubling Time Measured by 3D-Ultrasound. Med Sci Monit. 2017;23:3147–53.CrossRefPubMedPubMedCentral
34.
go back to reference Girometti R, Zanotel M, Londero V, Linda A, Lorenzon M, Zuiani C. Automated breast volume scanner (ABVS) in assessing breast cancer size: A comparison with conventional ultrasound and magnetic resonance imaging. Eur Radiol. 2017. Girometti R, Zanotel M, Londero V, Linda A, Lorenzon M, Zuiani C. Automated breast volume scanner (ABVS) in assessing breast cancer size: A comparison with conventional ultrasound and magnetic resonance imaging. Eur Radiol. 2017.
Metadata
Title
Does breast cancer growth rate really depend on tumor subtype? Measurement of tumor doubling time using serial ultrasonography between diagnosis and surgery
Authors
Kazuaki Nakashima
Takayoshi Uematsu
Kaoru Takahashi
Seiichirou Nishimura
Yukiko Tadokoro
Tomomi Hayashi
Takashi Sugino
Publication date
01-03-2019
Publisher
Springer Japan
Published in
Breast Cancer / Issue 2/2019
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-018-0914-0

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