PI3K/Akt/mTOR signalling pathway activation in patients with ER-positive, metachronous, contralateral breast cancer treated with hormone therapy

Abstract Background Estimates of contralateral breast cancer (CBC) risk in the modern treatment era by year of diagnosis and characteristics of the first breast cancer are needed to assess the impact of recent advances in breast cancer treatment and inform clinical decision making. Methods We examined CBC risk among 419,818 women (age 30–84 years) who were diagnosed with a first unilateral invasive breast cancer and survived ≥ 1 year in the US Surveillance, Epidemiology, and End Results program cancer registries from 1992 to 2015 (follow-up through 2016). CBC was defined as a second invasive breast cancer in the contralateral breast ≥ 12 months after the first breast cancer. We estimated standardized incidence ratios (SIRs) of CBC by year of diagnosis, age at diagnosis, and tumor characteristics for the first breast cancer. Cumulative incidence of CBC was calculated for women diagnosed with a first breast cancer in the recent treatment era (2004–2015, follow-up through 2016). Results Over a median follow-up of 8 years (range 1–25 years), 12,986 breast cancer patients developed CBC. Overall, breast cancer patients had approximately twice the risk of developing cancer in the contralateral breast when compared to that expected in the general population (SIR = 2.21, 95% CI = 2.17–2.25). SIRs for CBC declined by year of first diagnosis, irrespective of age at diagnosis and estrogen receptor (ER) status (p-trends < 0.001), but the strongest decline was after an ER-positive tumor. The 5-year cumulative incidence of CBC ranged from 1.01% (95% CI = 0.90–1.14%) in younger women (age < 50 years) with a first ER-positive tumor to 1.89% (95% CI = 1.61–2.21%) in younger women with a first ER-negative tumor. Conclusion Declines in CBC risk are consistent with continued advances in breast cancer treatment. The updated estimates of cumulative incidence inform breast cancer patients and clinicians on the risk of CBC and may help guide treatment decisions.

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Declining Incidence of Contralateral Breast Cancer in the United States From 1975 to 2006

Journal of Clinical Oncology ◽

10.1200/jco.2010.32.7395 ◽

2011 ◽

Vol 29 (12) ◽

pp. 1564-1569 ◽

Cited By ~ 144

Author(s):

Hazel B. Nichols ◽

Amy Berrington de González ◽

James V. Lacey ◽

Philip S. Rosenberg ◽

William F. Anderson

Keyword(s):

Breast Cancer ◽

United States ◽

Contralateral Breast Cancer ◽

Temporal Trends ◽

The United States ◽

Incidence Rates ◽

Contralateral Breast ◽

Breast Cancers ◽

Annual Percent Change ◽

Er Positive

Purpose Contralateral breast cancer (CBC) is the most frequent new malignancy among women diagnosed with a first breast cancer. Although temporal trends for first breast cancers have been well studied, trends for CBC are not so well established. Patients and Methods We examined temporal trends in CBC incidence using US Surveillance, Epidemiology, and End Results database (1975 to 2006). Data were stratified by estrogen receptor (ER) status of the first breast cancer for the available time period (1990+). We estimated the annual percent change (EAPC) in CBC rates using Poisson regression models adjusted for the age at and time since first breast cancer diagnosis. Results Before 1985, CBC incidence rates were stable (EAPC, 0.27% per year; 95% CI, −0.4 to 0.9), after which they declined with an EAPC of −3.07% per year (95% CI, −3.5 to −2.7). From 1990 forward, the declines were restricted to CBC after an ER-positive cancer (EAPC, −3.18%; 95% CI, −4.2 to −2.2) with no clear decreases after an ER-negative cancer. Estimated current age-specific CBC rates (per 100/year) after an ER-positive first cancer were: 0.45 for first cancers diagnosed before age 30 years and 0.25 to 0.37 for age 30 years or older. Rates after an ER-negative cancer were higher: 1.26 before age 30 years, 0.85 for age 30 to 35 years, and 0.45 to 0.65 for age 40 or older. Conclusion Results show a favorable decrease of 3% per year for CBC incidence in the United States since 1985. This overall trend was driven by declining CBC rates after an ER-positive cancer, possibly because of the widespread usage of adjuvant hormone therapies, after the results of the Nolvadex Adjuvant Trial Organisation were published in 1983, and/or other adjuvant treatments.

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Hormone Receptor Status of a Contralateral Breast Cancer Is Independent of the Receptor Status of the First Primary in Patients Not Receiving Adjuvant Tamoxifen

Journal of Clinical Oncology ◽

10.1200/jco.2005.04.076 ◽

2005 ◽

Vol 23 (21) ◽

pp. 4687-4694 ◽

Cited By ~ 25

Author(s):

G. Arpino ◽

H.L. Weiss ◽

G.M. Clark ◽

S.G. Hilsenbeck ◽

C.K. Osborne

Keyword(s):

Breast Cancer ◽

Adjuvant Therapy ◽

Hormone Receptor ◽

Contralateral Breast Cancer ◽

Hormone Receptor Status ◽

Contralateral Breast ◽

Adjuvant Tamoxifen ◽

Receptor Status ◽

Er Positive ◽

Median Interval

Purpose To determine whether the hormone receptor status of the primary breast cancer (PBC) is predictive of the hormone receptor status of the subsequent contralateral breast cancer (CBC). Patients and Methods We identified patients in our database with known estrogen receptor (ER; n = 193) and/or progesterone receptor (PgR; n = 178) status in their PBC and in their subsequent CBC. One hundred twenty-six of these patients had received no adjuvant therapy, 34 had received adjuvant tamoxifen, and 33 had received adjuvant chemotherapy alone. The median interval between the first diagnosis of PBC and the development of the subsequent CBC was 3 years. ER and PgR assays were assessed biochemically in two central reference laboratories using identical quality-controlled ligand-binding methods. Results Among systemically untreated patients (n = 126), 88% of patients with ER-positive PBC and 75% of patients with ER-negative PBC developed an ER-positive CBC (P = .11). Among the tamoxifen-treated patients, those with an ER-positive PBC were almost equally likely to develop an ER-positive (47%) or ER-negative (53%) CBC (P = .99). PgR status was similar. In the untreated group (n = 112), 59% of patients with a PgR-positive PBC and 66% with a PgR-negative PBC developed a PgR-positive CBC (P = .48). Among tamoxifen-treated patients (n = 33), 50% of patients with a PgR-positive PBC versus 27% of patients with a PgR-negative PBC developed a PgR-positive CBC (P = .28). Conclusion ER and PgR status of the primary tumor does not predict the hormone receptor status of the subsequent CBC in the absence of selective pressure of adjuvant therapy. Thus, other reasons should be considered to clarify the failure of tamoxifen to reduce the incidence of CBC in patients with a receptor-negative PBC.

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