Study of Changes in Estrogen Levels and Grip Strength in Postmenopausal Women Who Have Received 4 to 6 Years of Hormone Therapy for Breast Cancer and Are Currently Receiving Letrozole on Clinical Trial IBCSG-35-07

OBJECTIVES:

Primary

* To determine the serum level of estrogens (Estradiol \[E2\], Estrone \[E1\], and Estrone Sulphate \[E1S\] and sex hormone binding globulin \[SHBG\]) in postmenopausal women with prior endocrine-responsive, node-positive, resectable breast cancer completing 4 to 6 years of adjuvant endocrine therapy and enrolled on clinical trial IBCSG-35-07 receiving letrozole.
* To determine the degree of recovery of E2, E1, and E1S during the 3-month letrozole-off gap.

Secondary

* To determine the association between estrogen level changes and the clinical outcomes of toxicity and quality of life.
* To determine the effect of prior adjuvant endocrine therapy, age, body mass index, and type of menopause on estrogen levels.
* To determine the variability of estrogen level changes and its association with germline single nucleotide polymorphisms.
* To examine changes in grip-strength score.

OUTLINE: This is a multicenter study.

All patients undergo blood sample collection at baseline for the analysis of single nucleotide polymorphisms, after randomization on clinical trial IBCSG-35-07 and prior to the beginning treatment on IBCSG-35-07. Patients also undergo serum collection at baseline and at 9, 10.5, and 12 months for the analysis of estrogen levels and sex hormone binding globulins. Patients undergo measurement of grip strength at baseline and at 9 and 12 months. Samples may be banked for future research studies.

Patients complete quality-of-life questionnaires (Breast Cancer Prevention Trial \[BCPT\] Symptom Scales on Form 35-PRS and IBCSG Trial 35-07 QL Form) periodically.

• polymorphism analysis (Genetic): SNPs will be genotyped in whole blood samples taken at baseline.
• laboratory biomarker analysis (Other): Biomarkers will be assessed in blood and serum samples at different time points.
• quality-of-life assessment (Procedure): Quality of life will be assessed using the Breast Cancer Prevention Trial (BCPT) Symptom Scales and the IBCSG Trial 35-07 QL Form.

Primary outcomes

• Levels of Estrone (E1), Estradiol (E2), and Estrone Sulphate (E1S) Among Patients in the Longitudinal Analysis Population [0 (baseline), 9, 10.5, and 12 months from randomization]: In SOLE-EST, levels of E1, E2, and E1S were summarized over time at 0 (baseline), 9, 10.5, and 12 months from randomization among patients in the longitudinal analysis population (N=90 with post-baseline sample).
• Percent Change of E1, E2, and E1S Levels at 9, 10.5, and 12 Months From Baseline, by Treatment Group [9, 10.5, and 12 months from baseline]: Changes in hormone levels (E1, E2, and E1S levels), as percentage change over time according to treatment assignment (at 9, 10.5 and 12 months from baseline).

Secondary outcomes

• Toxicity Grade Changes for Arthralgia, Hot Flushes, and Insomnia [6 and 12 months]: Toxicity grade changes from 6 to 12 months (hot flashes, insomnia and arthralgia; Common Terminology Criteria for Adverse Events (CTCAE) version 3 values 1- 4 grouped as no change, increase in grade \[worsening\] or decrease in grade \[improvement\])
• Quality of Life (QoL) Score Changes [6 and 12 months: Change is calculated from 12 months minus 6 months, therefore positive values indicate an improved condition and negative values indicate a declined condition]: All patients in SOLE-EST were assessed for symptom specific QoL. QoL changes from 6 to 12 months (sleep change, hot flushes, tiredness, difficulties of becoming aroused, loss of sexual interest, physical wellbeing and mood; LASA (linear analogue self-assessment) scores 0-100 (higher is better QoL) were calculated as 12 months minus 6 months, so that negative is worsening and positive is improvement.
• Change in Grip-strength Score in the Dominant Hand [Changes in grip strength score is calculated at 12 months minus 9 months]: Grip strength was measured using the Martin Vigorimeter (a modified sphygmomanometer which measures the force of compression in kilo pascal by means of a compressible rubber ball). To perform the hand grip test, the patients were asked to squeeze the ball of a modified sphygmomanometer three times with maximal force and the maximal value of three trials of each hand were used for evaluation. Higher value represents greater strength, thus changes are calculated as 12 months minus 9 months so that positive is improved condition and negative is declined condition.

Sex: Female, ages: 18 Years to 120 Years

DISEASE CHARACTERISTICS:

* Previously diagnosed with breast cancer

  * Endocrine-responsive, node-positive, resectable disease
* Disease-free following 4-6 years of prior adjuvant endocrine therapy with selective estrogen-receptor modulators and/or aromatase inhibitors
* Patient must be currently enrolled on clinical trial IBCSG-35-07 as well as the Quality-of-Life substudy
* Hormone receptor status not specified

PATIENT CHARACTERISTICS:

* Postmenopausal

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics

Participant flow

Outcome results

• Levels of Estrone (E1), Estradiol (E2), and Estrone Sulphate (E1S) Among Patients in the Longitudinal Analysis Population (Primary), Median, pg/mL: Continuous Letrozole Treatment Group (Baseline, Month 0) 12.4 (9.7 to 23.4); Intermittent Letrozole Treatment Group (Baseline, Month 0) 14.3 (5.8 to 26.1); Continuous Letrozole Treatment Group (9 Months) 4.8 (4.2 to 5.5); Intermittent Letrozole Treatment Group (9 Months) 5.1 (4.3 to 5.8); Continuous Letrozole Treatment Group (10.5 Months) 4.7 (3.9 to 5.5); Intermittent Letrozole Treatment Group (10.5 Months) 21.6 (15.4 to 29.7); Continuous Letrozole Treatment Group (12 Months) 5.1 (4.4 to 7.0); Intermittent Letrozole Treatment Group (12 Months) 26.8 (18.5 to 35.7)
• Percent Change of E1, E2, and E1S Levels at 9, 10.5, and 12 Months From Baseline, by Treatment Group (Primary), Median, percentage change: Continuous Letrozole Treamtnet Group (9 Months) -58.2 (-77.2 to -44.9); Intermittent Letrozole Treatment Group (9 Months) -59.3 (-79.4 to -13.9); Continuous Letrozole Treatment Arm (10.5 Months) -67.3 (-81.1 to -53.0); Intermittent Letrozole Treatment Group (10.5 Months) 76.6 (-22.7 to 289.3); Continuous Letrozole Treatment Arm (12 Months) -57.8 (-75.4 to -34.8); Intermittent Letrozole Treatment Group (12 Months) 68.7 (-14.4 to 318.9)
• Toxicity Grade Changes for Arthralgia, Hot Flushes, and Insomnia (Secondary), Median, toxicity grade: Continuous Letrozole Treatment Group 0.0 (0.0 to 0.0); Intermittent Letrozole Treatment Group 0.0 (0.0 to 0.0)
• Quality of Life (QoL) Score Changes (Secondary), Median, score on a scale: Continuous Letrozole Treatment Group 0.0 (-6.5 to 14.5); Intermittent Letrozole Treatment Group -9.5 (-27.0 to 2.0)
• Change in Grip-strength Score in the Dominant Hand (Secondary), Median, kilopascals: Continuous Letrozole Treatment Group -1.0 (-6.0 to 2.0); Intermittent Letrozole Treatment Group 0.0 (-6.0 to 4.0)

Adverse events

Time frame: Adverse event (AE) information were collected at baseline and at 6 and 12 months in the SOLE main study.

Limitations and caveats: After 5 years of adjuvant endocrine therapy, resistant tumoral cells could be different from those present at initial diagnosis, and the apoptotic effect of estrogen on these cells might be insufficient. It is possible that the intermittent treatment was given too late.

• Study Protocol (PDF, 2010-10-26)
• Statistical Analysis Plan (PDF, 2020-03-01)

• Jacquie Chirgwin, MD, Study chair, Box Hill Hospital
• Guy Jerusalem, MD, PhD, Study chair, CHU Liege - Domaine Universitaire du Sart Tilman