Revisiting the definition of estrogen receptor positivity in HER2-negative primary breast cancer

T. Fujii, T. Kogawa, W. Dong, A. A. Sahin, S. Moulder, J. K. Litton, D. Tripathy, Takayuki Iwamoto, K. K. Hunt, L. Pusztai, B. Lim, Y. Shen, Naoto T. Ueno

Research output: Contribution to journalArticle

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Abstract

Background: Although 1% has been used as cut-off for estrogen receptor (ER) positivity, several studies have reported that tumors with ER < 1% have characteristics similar to those with 1% ≤ ER < 10%. We hypothesized that in patients with human epidermal growth factor 2 (HER 2)-negative breast cancer, a cut-off of 10% is more useful than one of 1% in discriminating for both a better pathological complete response (pCR) rate to neoadjuvant chemotherapy and a better long-term outcome with adjuvant hormonal therapy. Our objectives were to identify a percentage of ER expression below which pCR was likely and to determine whether this cut-off value can identify patients who would benefit from adjuvant hormonal therapy. Patients and methods: Patients with stage II or III HER 2-negative primary breast cancer who received neoadjuvant chemotherapy followed by definitive surgery between June 1982 and June 2013 were included. Logistic regression models were used to assess the association between each variable and pCR. Cox models were used to analyze time to recurrence and overall survival. The recursive partitioning and regression trees method was used to calculate the cut-off value of ER expression. Results: A total of 3055 patients were analyzed. Low percentage of ER was significantly associated with high pCR rate (OR = 0.99, 95% CI = 0.986-0.994, P < 0.001). The recommended cut-off of ER expression below which pCR was likely was 9.5%. Among patients with ER ≥ 10% tumors, but not those with 1% ≤ ER < 10% tumors, adjuvant hormonal therapy was significantly associated with long time to recurrence (HR = 0.24, 95% CI = 0.16-0.36, P < 0.001) and overall survival (HR = 0.32, 95% CI = 0.2-0.5, P < 0.001). Conclusion: Stage II or III HER 2-negative primary breast cancer with ER < 10% behaves clinically like triple-negative breast cancer in terms of pCR and survival outcomes and patients with such tumors may have a limited benefit from adjuvant hormonal therapy. It may be more clinically relevant to define triple-negative breast cancer as HER2-negative breast cancer with <10%, rather than <1%, of ER and/or progesterone receptor expression.

Original languageEnglish
Pages (from-to)2420-2428
Number of pages9
JournalAnnals of Oncology
Volume28
Issue number10
DOIs
Publication statusPublished - Jan 1 2017

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Estrogen Receptors
Breast Neoplasms
Epidermal Growth Factor
Triple Negative Breast Neoplasms
Survival
Neoplasms
Logistic Models
Recurrence
Drug Therapy
Progesterone Receptors
Therapeutics
Proportional Hazards Models

Keywords

  • Adjuvant hormonal therapy
  • Breast cancer
  • ER positivity
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Fujii, T., Kogawa, T., Dong, W., Sahin, A. A., Moulder, S., Litton, J. K., ... Ueno, N. T. (2017). Revisiting the definition of estrogen receptor positivity in HER2-negative primary breast cancer. Annals of Oncology, 28(10), 2420-2428. https://doi.org/10.1093/annonc/mdx397

Revisiting the definition of estrogen receptor positivity in HER2-negative primary breast cancer. / Fujii, T.; Kogawa, T.; Dong, W.; Sahin, A. A.; Moulder, S.; Litton, J. K.; Tripathy, D.; Iwamoto, Takayuki; Hunt, K. K.; Pusztai, L.; Lim, B.; Shen, Y.; Ueno, Naoto T.

In: Annals of Oncology, Vol. 28, No. 10, 01.01.2017, p. 2420-2428.

Research output: Contribution to journalArticle

Fujii, T, Kogawa, T, Dong, W, Sahin, AA, Moulder, S, Litton, JK, Tripathy, D, Iwamoto, T, Hunt, KK, Pusztai, L, Lim, B, Shen, Y & Ueno, NT 2017, 'Revisiting the definition of estrogen receptor positivity in HER2-negative primary breast cancer', Annals of Oncology, vol. 28, no. 10, pp. 2420-2428. https://doi.org/10.1093/annonc/mdx397
Fujii, T. ; Kogawa, T. ; Dong, W. ; Sahin, A. A. ; Moulder, S. ; Litton, J. K. ; Tripathy, D. ; Iwamoto, Takayuki ; Hunt, K. K. ; Pusztai, L. ; Lim, B. ; Shen, Y. ; Ueno, Naoto T. / Revisiting the definition of estrogen receptor positivity in HER2-negative primary breast cancer. In: Annals of Oncology. 2017 ; Vol. 28, No. 10. pp. 2420-2428.
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abstract = "Background: Although 1{\%} has been used as cut-off for estrogen receptor (ER) positivity, several studies have reported that tumors with ER < 1{\%} have characteristics similar to those with 1{\%} ≤ ER < 10{\%}. We hypothesized that in patients with human epidermal growth factor 2 (HER 2)-negative breast cancer, a cut-off of 10{\%} is more useful than one of 1{\%} in discriminating for both a better pathological complete response (pCR) rate to neoadjuvant chemotherapy and a better long-term outcome with adjuvant hormonal therapy. Our objectives were to identify a percentage of ER expression below which pCR was likely and to determine whether this cut-off value can identify patients who would benefit from adjuvant hormonal therapy. Patients and methods: Patients with stage II or III HER 2-negative primary breast cancer who received neoadjuvant chemotherapy followed by definitive surgery between June 1982 and June 2013 were included. Logistic regression models were used to assess the association between each variable and pCR. Cox models were used to analyze time to recurrence and overall survival. The recursive partitioning and regression trees method was used to calculate the cut-off value of ER expression. Results: A total of 3055 patients were analyzed. Low percentage of ER was significantly associated with high pCR rate (OR = 0.99, 95{\%} CI = 0.986-0.994, P < 0.001). The recommended cut-off of ER expression below which pCR was likely was 9.5{\%}. Among patients with ER ≥ 10{\%} tumors, but not those with 1{\%} ≤ ER < 10{\%} tumors, adjuvant hormonal therapy was significantly associated with long time to recurrence (HR = 0.24, 95{\%} CI = 0.16-0.36, P < 0.001) and overall survival (HR = 0.32, 95{\%} CI = 0.2-0.5, P < 0.001). Conclusion: Stage II or III HER 2-negative primary breast cancer with ER < 10{\%} behaves clinically like triple-negative breast cancer in terms of pCR and survival outcomes and patients with such tumors may have a limited benefit from adjuvant hormonal therapy. It may be more clinically relevant to define triple-negative breast cancer as HER2-negative breast cancer with <10{\%}, rather than <1{\%}, of ER and/or progesterone receptor expression.",
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AU - Fujii, T.

AU - Kogawa, T.

AU - Dong, W.

AU - Sahin, A. A.

AU - Moulder, S.

AU - Litton, J. K.

AU - Tripathy, D.

AU - Iwamoto, Takayuki

AU - Hunt, K. K.

AU - Pusztai, L.

AU - Lim, B.

AU - Shen, Y.

AU - Ueno, Naoto T.

PY - 2017/1/1

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N2 - Background: Although 1% has been used as cut-off for estrogen receptor (ER) positivity, several studies have reported that tumors with ER < 1% have characteristics similar to those with 1% ≤ ER < 10%. We hypothesized that in patients with human epidermal growth factor 2 (HER 2)-negative breast cancer, a cut-off of 10% is more useful than one of 1% in discriminating for both a better pathological complete response (pCR) rate to neoadjuvant chemotherapy and a better long-term outcome with adjuvant hormonal therapy. Our objectives were to identify a percentage of ER expression below which pCR was likely and to determine whether this cut-off value can identify patients who would benefit from adjuvant hormonal therapy. Patients and methods: Patients with stage II or III HER 2-negative primary breast cancer who received neoadjuvant chemotherapy followed by definitive surgery between June 1982 and June 2013 were included. Logistic regression models were used to assess the association between each variable and pCR. Cox models were used to analyze time to recurrence and overall survival. The recursive partitioning and regression trees method was used to calculate the cut-off value of ER expression. Results: A total of 3055 patients were analyzed. Low percentage of ER was significantly associated with high pCR rate (OR = 0.99, 95% CI = 0.986-0.994, P < 0.001). The recommended cut-off of ER expression below which pCR was likely was 9.5%. Among patients with ER ≥ 10% tumors, but not those with 1% ≤ ER < 10% tumors, adjuvant hormonal therapy was significantly associated with long time to recurrence (HR = 0.24, 95% CI = 0.16-0.36, P < 0.001) and overall survival (HR = 0.32, 95% CI = 0.2-0.5, P < 0.001). Conclusion: Stage II or III HER 2-negative primary breast cancer with ER < 10% behaves clinically like triple-negative breast cancer in terms of pCR and survival outcomes and patients with such tumors may have a limited benefit from adjuvant hormonal therapy. It may be more clinically relevant to define triple-negative breast cancer as HER2-negative breast cancer with <10%, rather than <1%, of ER and/or progesterone receptor expression.

AB - Background: Although 1% has been used as cut-off for estrogen receptor (ER) positivity, several studies have reported that tumors with ER < 1% have characteristics similar to those with 1% ≤ ER < 10%. We hypothesized that in patients with human epidermal growth factor 2 (HER 2)-negative breast cancer, a cut-off of 10% is more useful than one of 1% in discriminating for both a better pathological complete response (pCR) rate to neoadjuvant chemotherapy and a better long-term outcome with adjuvant hormonal therapy. Our objectives were to identify a percentage of ER expression below which pCR was likely and to determine whether this cut-off value can identify patients who would benefit from adjuvant hormonal therapy. Patients and methods: Patients with stage II or III HER 2-negative primary breast cancer who received neoadjuvant chemotherapy followed by definitive surgery between June 1982 and June 2013 were included. Logistic regression models were used to assess the association between each variable and pCR. Cox models were used to analyze time to recurrence and overall survival. The recursive partitioning and regression trees method was used to calculate the cut-off value of ER expression. Results: A total of 3055 patients were analyzed. Low percentage of ER was significantly associated with high pCR rate (OR = 0.99, 95% CI = 0.986-0.994, P < 0.001). The recommended cut-off of ER expression below which pCR was likely was 9.5%. Among patients with ER ≥ 10% tumors, but not those with 1% ≤ ER < 10% tumors, adjuvant hormonal therapy was significantly associated with long time to recurrence (HR = 0.24, 95% CI = 0.16-0.36, P < 0.001) and overall survival (HR = 0.32, 95% CI = 0.2-0.5, P < 0.001). Conclusion: Stage II or III HER 2-negative primary breast cancer with ER < 10% behaves clinically like triple-negative breast cancer in terms of pCR and survival outcomes and patients with such tumors may have a limited benefit from adjuvant hormonal therapy. It may be more clinically relevant to define triple-negative breast cancer as HER2-negative breast cancer with <10%, rather than <1%, of ER and/or progesterone receptor expression.

KW - Adjuvant hormonal therapy

KW - Breast cancer

KW - ER positivity

KW - Triple-negative breast cancer

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