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Published in: Discover Oncology 3-4/2020

01-08-2020 | Breast Cancer | Original Paper

Estrogen Receptor Positive and Progesterone Receptor Negative Breast Cancer: the Role of Hormone Therapy

Authors: Robert Dembinski, Vishnu Prasath, Carisa Bohnak, Charalampos Siotos, Mohamad E. Sebai, Kevin Psoter, Faiz Gani, Joe Canner, Melissa S. Camp, Armina Azizi, Lisa Jacobs, Mehran Habibi

Published in: Discover Oncology | Issue 3-4/2020

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Abstract

ER+/PR− (estrogen receptor positive and progesterone receptor negative) tumors constitute only a small portion of the breast cancer population. Patients with ER+/PR− tumors, however, are characterized by worse survival compared to patients with ER+/PR+ (estrogen receptor positive and progesterone receptor positive) tumors. Controversy exists regarding the efficacy of hormone blocking therapy for patients with ER+/PR− tumors. The NCDB was queried between 2004 and 2015, and patients with invasive ER+/PR− tumors were identified. We employed univariate Cox proportional hazards to compare outcomes among patients that did or did not receive hormone blocking therapy. We identified 138,398 patients with invasive ER+/PR− tumors, 32,044 (23%) of whom did not receive hormone blocking therapy. The reasons for not receiving hormone blocking therapy included contraindications to treatment, death, patient refusal, and unknown. There were no significant differences in race, income quartile, or education quartile between patients who did and did not receive hormone blocking therapy. Patients who did not receive hormone blocking therapy underwent surgical assessment of the axilla more frequently than those who did receive hormone therapy. Our analysis demonstrated that hormone blocking therapy administration was associated with increased overall survival for up to 10 years of follow up (HR: 0.58; 95% CI: 0.56–0.59, p < 0.001). Hormone blocking therapy may be associated with increased survival for breast cancer patients with ER+/PR− tumors. Although this benefit may last for years after completion of the course, up to 25% of patients do not receive this treatment. Strategies to increase the utilization and adherence to hormone blocking therapy regimens may improve patient survival outcomes.
Literature
1.
2.
go back to reference Arpino G et al (2005) Estrogen receptor–positive, progesterone receptor–negative breast cancer: association with growth factor receptor expression and Tamoxifen Resistance. J Natl Cancer Inst. 97(17):1254–1261PubMedCrossRef Arpino G et al (2005) Estrogen receptor–positive, progesterone receptor–negative breast cancer: association with growth factor receptor expression and Tamoxifen Resistance. J Natl Cancer Inst. 97(17):1254–1261PubMedCrossRef
3.
go back to reference Clark GM, McGuire WL (1988) Steroid receptors and other prognostic factors in primary breast cancer. Semin Oncol. 15:20–25PubMed Clark GM, McGuire WL (1988) Steroid receptors and other prognostic factors in primary breast cancer. Semin Oncol. 15:20–25PubMed
4.
go back to reference Bae SY et al (2015) Poor prognosis of single hormone receptor-positive breast cancer: similar outcome as triple-negative breast cancer. BMC Cancer. 15(1):138PubMedPubMedCentralCrossRef Bae SY et al (2015) Poor prognosis of single hormone receptor-positive breast cancer: similar outcome as triple-negative breast cancer. BMC Cancer. 15(1):138PubMedPubMedCentralCrossRef
5.
go back to reference Clahsen PC et al (1999) The utility of mitotic index, estrogen receptor and Ki-67 measurements in the creation of novel prognostic indices for node-negative breast cancer. Eur J Surg Oncol. 25(4):356–363.sPubMedCrossRef Clahsen PC et al (1999) The utility of mitotic index, estrogen receptor and Ki-67 measurements in the creation of novel prognostic indices for node-negative breast cancer. Eur J Surg Oncol. 25(4):356–363.sPubMedCrossRef
6.
go back to reference McGuir WL (1986) Prognostic factors in primary breast cancer. Cancer Surv. 5(3):527–536 McGuir WL (1986) Prognostic factors in primary breast cancer. Cancer Surv. 5(3):527–536
7.
go back to reference Fisher B et al (1988) Relative worth of estrogen or progesterone receptor and pathologic characteristics of differentiation as indicators of prognosis in node negative breast cancer patients: findings from National Surgical Adjuvant Breast and Bowel Project Protocol B-06. J Clin Oncol. 6(7):1076–1087PubMedCrossRef Fisher B et al (1988) Relative worth of estrogen or progesterone receptor and pathologic characteristics of differentiation as indicators of prognosis in node negative breast cancer patients: findings from National Surgical Adjuvant Breast and Bowel Project Protocol B-06. J Clin Oncol. 6(7):1076–1087PubMedCrossRef
8.
go back to reference Grann VR et al (2005) Hormone receptor status and survival in a population-based cohort of patients with breast carcinoma. Cancer. 103(11):2241–2251PubMedCrossRef Grann VR et al (2005) Hormone receptor status and survival in a population-based cohort of patients with breast carcinoma. Cancer. 103(11):2241–2251PubMedCrossRef
9.
go back to reference Gasparini G (1998) Prognostic variables in node-negative and node-positive breast cancer. Breast Cancer Res Treat. 52(1–3):321–331PubMedCrossRef Gasparini G (1998) Prognostic variables in node-negative and node-positive breast cancer. Breast Cancer Res Treat. 52(1–3):321–331PubMedCrossRef
10.
go back to reference Jensen EV, Jacobson HI (2010) Estrogen action: a historic perspective on the implications of considering alternative approaches. Physiol Behav. 99(2):151–162PubMedCrossRef Jensen EV, Jacobson HI (2010) Estrogen action: a historic perspective on the implications of considering alternative approaches. Physiol Behav. 99(2):151–162PubMedCrossRef
11.
go back to reference Jordan VC, Jaspan T (1976) Tamoxifen as an anti-tumor agent: estrogen binding as a predictive test for tumor response. J Endocrinol. 68(3):453–460PubMedCrossRef Jordan VC, Jaspan T (1976) Tamoxifen as an anti-tumor agent: estrogen binding as a predictive test for tumor response. J Endocrinol. 68(3):453–460PubMedCrossRef
12.
go back to reference Mauri FA et al (1999) Prognostic value of estrogen receptor status can be improved by combined evaluation of p53, Bcl2 and PgR expression: an immunohistochemical study on breast carcinoma with long-term follow-up. Int J Oncol 15(6):1137–1147PubMed Mauri FA et al (1999) Prognostic value of estrogen receptor status can be improved by combined evaluation of p53, Bcl2 and PgR expression: an immunohistochemical study on breast carcinoma with long-term follow-up. Int J Oncol 15(6):1137–1147PubMed
13.
go back to reference Moore DD (2012) A conversation with Elwood Jensen. Annu Rev Physiol. 74(1):1–11CrossRef Moore DD (2012) A conversation with Elwood Jensen. Annu Rev Physiol. 74(1):1–11CrossRef
14.
go back to reference Banerjee M et al (2004) Tree-based model for breast cancer prognostication. J Clin Oncol. 22(13):2567–2575PubMedCrossRef Banerjee M et al (2004) Tree-based model for breast cancer prognostication. J Clin Oncol. 22(13):2567–2575PubMedCrossRef
15.
go back to reference Giuliano AE et al (2017) Breast cancer—major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 67(4):290–303PubMedCrossRef Giuliano AE et al (2017) Breast cancer—major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 67(4):290–303PubMedCrossRef
16.
go back to reference Sun J-Y et al (2016) Progesterone receptor loss identifies hormone receptor-positive and HER2-negative breast cancer subgroups at higher risk of relapse: a retrospective cohort study. OncoTargets Ther. 9:1707–1713 Sun J-Y et al (2016) Progesterone receptor loss identifies hormone receptor-positive and HER2-negative breast cancer subgroups at higher risk of relapse: a retrospective cohort study. OncoTargets Ther. 9:1707–1713
17.
go back to reference Bardou V-J et al (2003) Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases. J Clin Oncol. 21(10):1973–1979PubMedCrossRef Bardou V-J et al (2003) Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases. J Clin Oncol. 21(10):1973–1979PubMedCrossRef
18.
go back to reference Thakkar JP, Mehta DG (2011) A review of an unfavorable subset of breast cancer: estrogen receptor positive progesterone receptor negative. Oncologist. 16(3):276–285PubMedPubMedCentralCrossRef Thakkar JP, Mehta DG (2011) A review of an unfavorable subset of breast cancer: estrogen receptor positive progesterone receptor negative. Oncologist. 16(3):276–285PubMedPubMedCentralCrossRef
19.
go back to reference Dunnwald LK, Rossing MA, Christopher I Li. (2007) Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients. Breast Cancer Res. 9(1):R6PubMedPubMedCentralCrossRef Dunnwald LK, Rossing MA, Christopher I Li. (2007) Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients. Breast Cancer Res. 9(1):R6PubMedPubMedCentralCrossRef
20.
go back to reference Early Breast Cancer Trialists’ Collaborative Group (2005) Effects of chemotherapy and hormone therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials. Lancet. 365(9472):1687–1717CrossRef Early Breast Cancer Trialists’ Collaborative Group (2005) Effects of chemotherapy and hormone therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials. Lancet. 365(9472):1687–1717CrossRef
21.
go back to reference Lumachi F, Santeufemia DA, Basso SM (1996) Current medical treatment of estrogen receptor-positive breast cancer. Biol Chem. 6(3):231–239 Lumachi F, Santeufemia DA, Basso SM (1996) Current medical treatment of estrogen receptor-positive breast cancer. Biol Chem. 6(3):231–239
22.
go back to reference Bezwoda WR, Esser JD, Dansey R, Kessel I, Lange M (1991) The value of estrogen and progesterone receptor determinations in advanced breast cancer. Estrogen receptor level but not progesterone receptor level correlates with response to tamoxifen. Cancer. 68(4):867–872PubMedCrossRef Bezwoda WR, Esser JD, Dansey R, Kessel I, Lange M (1991) The value of estrogen and progesterone receptor determinations in advanced breast cancer. Estrogen receptor level but not progesterone receptor level correlates with response to tamoxifen. Cancer. 68(4):867–872PubMedCrossRef
23.
go back to reference Early Breast Cancer Trialists’ Collaborative Group (2005) Effects of chemotherapy and hormone therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials. Lancet. 365(9472):1687–1717CrossRef Early Breast Cancer Trialists’ Collaborative Group (2005) Effects of chemotherapy and hormone therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials. Lancet. 365(9472):1687–1717CrossRef
24.
go back to reference Dowsett M et al (2006) Benefit from adjuvant tamoxifen therapy in primary breast cancer patients according estrogen receptor, progesterone receptor, EGF receptor and HER2 status. Ann Oncol. 17(5):818–826PubMedCrossRef Dowsett M et al (2006) Benefit from adjuvant tamoxifen therapy in primary breast cancer patients according estrogen receptor, progesterone receptor, EGF receptor and HER2 status. Ann Oncol. 17(5):818–826PubMedCrossRef
25.
go back to reference Goldhirsch A et al (2009) Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009. Ann Oncol. 20(8):1319–1329PubMedPubMedCentralCrossRef Goldhirsch A et al (2009) Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009. Ann Oncol. 20(8):1319–1329PubMedPubMedCentralCrossRef
26.
go back to reference Lopez-Tarruella S, Schiff R (2007) The dynamics of estrogen receptor status in breast cancer: re-shaping the paradigm. Clin Cancer Res. 13(23):6921–6925PubMedCrossRef Lopez-Tarruella S, Schiff R (2007) The dynamics of estrogen receptor status in breast cancer: re-shaping the paradigm. Clin Cancer Res. 13(23):6921–6925PubMedCrossRef
27.
go back to reference Chlebowski RT, Aragaki AK, Anderson GL (2015) Menopausal hormone therapy influence on breast cancer outcomes in the Women’s Health Initiative. J Natl Compr Cancer Netw. 13(7):917–924CrossRef Chlebowski RT, Aragaki AK, Anderson GL (2015) Menopausal hormone therapy influence on breast cancer outcomes in the Women’s Health Initiative. J Natl Compr Cancer Netw. 13(7):917–924CrossRef
28.
go back to reference Tharmapalan P, Mahendralingam M, Berman HK, Khokha R (2019) Mammary stem cells and progenitors: targeting the roots of breast cancer for prevention. EMBO J. 38(14):e100852PubMedPubMedCentralCrossRef Tharmapalan P, Mahendralingam M, Berman HK, Khokha R (2019) Mammary stem cells and progenitors: targeting the roots of breast cancer for prevention. EMBO J. 38(14):e100852PubMedPubMedCentralCrossRef
29.
go back to reference King M-C, Wieand S, Hale K, Lee M, Walsh T, Owens K, Tait J et al (2001) Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. Jama. 286(18):2251–2256PubMedCrossRef King M-C, Wieand S, Hale K, Lee M, Walsh T, Owens K, Tait J et al (2001) Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. Jama. 286(18):2251–2256PubMedCrossRef
30.
go back to reference Fisher B, Costantino JP, Lawrence Wickerham D, Cecchini RS, Cronin WM, Robidoux A, Bevers TB et al (2005) Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst. 97(22):1652–1662PubMedCrossRef Fisher B, Costantino JP, Lawrence Wickerham D, Cecchini RS, Cronin WM, Robidoux A, Bevers TB et al (2005) Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst. 97(22):1652–1662PubMedCrossRef
31.
go back to reference Vogel VG, Costantino JP, Lawrence Wickerham D, Cronin WM, Cecchini RS, Atkins JN, Bevers TB et al (2006) Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. Jama. 295(23):2727–2741PubMedCrossRef Vogel VG, Costantino JP, Lawrence Wickerham D, Cronin WM, Cecchini RS, Atkins JN, Bevers TB et al (2006) Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. Jama. 295(23):2727–2741PubMedCrossRef
32.
go back to reference Vogel VG, Costantino JP, Lawrence Wickerham D, Cronin WM, Cecchini RS, Atkins JN, Bevers TB et al (2010) Update of the national surgical adjuvant breast and bowel project study of tamoxifen and raloxifene (STAR) P-2 trial: preventing breast cancer. Cancer Prev Res. 3(6):696–706CrossRef Vogel VG, Costantino JP, Lawrence Wickerham D, Cronin WM, Cecchini RS, Atkins JN, Bevers TB et al (2010) Update of the national surgical adjuvant breast and bowel project study of tamoxifen and raloxifene (STAR) P-2 trial: preventing breast cancer. Cancer Prev Res. 3(6):696–706CrossRef
33.
go back to reference Cuzick J, Sestak I, Cawthorn S, Hamed H, Holli K, Howell A, Forbes JF, Investigators IBIS-I (2015) Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. Lancet Oncol. 16(1):67–75PubMedPubMedCentralCrossRef Cuzick J, Sestak I, Cawthorn S, Hamed H, Holli K, Howell A, Forbes JF, Investigators IBIS-I (2015) Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. Lancet Oncol. 16(1):67–75PubMedPubMedCentralCrossRef
34.
go back to reference Goss PE, Ingle JN, Alés-Martínez JE, Cheung AM, Chlebowski RT, Wactawski-Wende J, McTiernan A et al (2011) Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med. 364(25):2381–2391PubMedCrossRef Goss PE, Ingle JN, Alés-Martínez JE, Cheung AM, Chlebowski RT, Wactawski-Wende J, McTiernan A et al (2011) Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med. 364(25):2381–2391PubMedCrossRef
35.
go back to reference Cuzick J, Sestak I, Forbes JF, Dowsett M, Knox J, Cawthorn S, Saunders C et al (2014) Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomized placebo-controlled trial. Lancet. 383(9922):1041–1048PubMedCrossRef Cuzick J, Sestak I, Forbes JF, Dowsett M, Knox J, Cawthorn S, Saunders C et al (2014) Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomized placebo-controlled trial. Lancet. 383(9922):1041–1048PubMedCrossRef
36.
go back to reference Osborne CK, Schiff R, Arpino G, Lee AS, Hilsenbeck VG (2005) Endocrine responsiveness: Understanding how progesterone receptor can be used to select endocrine therapy. Breast. 14(6):458–465PubMedCrossRef Osborne CK, Schiff R, Arpino G, Lee AS, Hilsenbeck VG (2005) Endocrine responsiveness: Understanding how progesterone receptor can be used to select endocrine therapy. Breast. 14(6):458–465PubMedCrossRef
37.
go back to reference Di G-h, Wu J, Lu J-s, Shen K-w, Liu G-y, Shen Z-z, Shao Z-M (2008) Breast cancer patients with estrogen receptor-negative/progesterone receptor-positive tumors: being younger and getting less benefit from adjuvant tamoxifen treatment. J Cancer Res Clin Oncol. 134(12):1347–1354PubMedCrossRef Di G-h, Wu J, Lu J-s, Shen K-w, Liu G-y, Shen Z-z, Shao Z-M (2008) Breast cancer patients with estrogen receptor-negative/progesterone receptor-positive tumors: being younger and getting less benefit from adjuvant tamoxifen treatment. J Cancer Res Clin Oncol. 134(12):1347–1354PubMedCrossRef
Metadata
Title
Estrogen Receptor Positive and Progesterone Receptor Negative Breast Cancer: the Role of Hormone Therapy
Authors
Robert Dembinski
Vishnu Prasath
Carisa Bohnak
Charalampos Siotos
Mohamad E. Sebai
Kevin Psoter
Faiz Gani
Joe Canner
Melissa S. Camp
Armina Azizi
Lisa Jacobs
Mehran Habibi
Publication date
01-08-2020
Publisher
Springer US
Published in
Discover Oncology / Issue 3-4/2020
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI
https://doi.org/10.1007/s12672-020-00387-1

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