Limited Adjuvant Endocrine Therapy for Low Risk Breast Cancer
Limited Adjuvant Endocrine Therapy for Low Risk Breast Cancer
Phase II trial of 2 years of standard adjuvant endocrine therapy after low risk hormone
 receptor positive, HER2 negative, node negative breast cancer in women older than 50 at
 diagnosis.

 The study hypothesis is that reducing adjuvant endocrine therapy from 5 to 2 years in a
 population with low risk of breast cancer; as determined by histopathologic criteria and
 confirmed by low risk genomic analysis using Prosigna®; will be safe and acceptable to this
 population, and will not compromise the expected excellent breast cancer specific outcomes
 for this population.
Women older than 50 at diagnosis of an invasive breast cancer which is all of: node
 negative/N0i+; T1 or T2; low or intermediate grade; with strong or intermediate expression of
 hormone receptors (ER and PR); and HER2 negative, and who have had adequate local therapy for
 their tumor, are invited to participate in Prosigna® screening. A sample of their excised
 tumor is sent for Prosigna® testing. This is a validated and widely approved genomic test to
 assess recurrence risk in hormone receptor positive/HER2 negative, node negative breast
 tumors. Tumors with a low risk result, defined as Risk of Recurrence (ROR) less than or equal
 to 40, are then eligible for enrollment on the LA LEAST study of 2 years of endocrine therapy
 (tamoxifen for pre/perimenopausal women and aromatase inhibitor for postmenopausal women). To
 mimic real life, there is flexibility to switch to an alternate standard of care endocrine
 therapy during the two years if intolerable side effects develop. During the two years of
 therapy, participants are seen every six months and complete periodic quality of life (QOL)
 questionnaires designed to measure quality of life, mood, side effects, and anxiety/fear of
 recurrence. Following two years of therapy, participants have annual study visits until year
 10, with similar questionnaires at some but not all time points, and assessment of study
 endpoints. Primary endpoint is the 5 year distant relapse free interval (DRFI), defined as
 freedom from distant recurrence or breast cancer death at five years. Secondary endpoints
 include longitudinal QOL comparisons, 10 year breast cancer free interval and 10 year
 contralateral breast cancer rate. It is anticipated that about 400 individuals will need to
 be screened to enroll 290 participants with requisite low score. The sample size is based on
 an expected 5 year DRFI of 96.8%, one sided alpha of 0.05 and a rejection of the alternate
 hypothesis if the lower boundary of the one sided confidence interval yields an observed DRFI
 below 95%.
Inclusion Criteria: for Prosigna® screening

 -  Diagnosis of invasive breast cancer which is:

 -  Unifocal or multifocal (not multicentric)

 -  Unilateral

 -  Moderate or strongly hormone receptor positive

 -  HER2 negative

 -  Ductal grade 1 or 2, or lobular any grade, or pure tubular (any grade) or pure
 papillary (any grade). If mixed lobular-ductal histology, the ductal component
 must be grade 1 or 2.

 -  Stage pT1N0 (tumor </= 20mm, negative node) or pT2N0 (tumor 21-50mm, node
 negative) or pT1N0i+ (tumor </=20mm and isolated tumor cells in node[s]) or
 pT2N0i+ (tumor 21-50mm and isolated tumor cells in node[s]) (see Appendix 2).
 Tumor size must be sufficient for Prosigna® testing. pNX (nodal status unknown)
 stage is not eligible.

 -  Subject must be female

 -  Subject must be age > 50 years at breast cancer diagnosis

 -  Subject may be pre, peri, or postmenopausal.

 -  Subject must have a > 5-year life expectancy based on physician judgement of subject's
 co-morbid illnesses and age

 -  Subject must undergo standard of care loco-regional management (sentinel node biopsy
 and/or axillary dissection; breast conserving surgery or mastectomy; radiation to
 breast following breast conserving surgery, with radiotherapy details per local
 institution practice). Surgery will have been no more than 24 weeks prior to endocrine
 therapy start. Subjects having repeat surgeries after radiation, regardless of
 indication, should count the date of last surgery that preceded radiation. Subjects
 may undergo Prosigna® screening prior to completion of radiation.

 -  The breast surgery will have achieved negative surgical margins. Tumours with positive
 margins that are not re-resectable are eligible if followed by radiation with a boost
 (partial mastectomy) or chest wall radiation (mastectomy)

 -  No (neoadjuvant or adjuvant) chemotherapy given or planned for this breast cancer

 -  No other non-breast cancer within the last 5 years, except non-melanoma skin cancer,
 melanoma in situ, cervix carcinoma in situ, and anal carcinoma in situ

 -  No prior hormone receptor positive invasive breast cancer. Prior contralateral DCIS
 treated with standard of care local therapy, and prior lobular carcinoma in situ
 (LCIS) are allowed, provided no endocrine therapy with any of tamoxifen, ovarian
 suppression, raloxifene, or aromatase inhibitor was given

 -  Subject will have not have started endocrine therapy prior to enrollment

 -  Subject has signed a screening informed consent form

 -  Subject has intent to be adherent to endocrine therapy for two years in the absence of
 serious toxicity

 Inclusion criteria for study enrollment:

 -  Prosigna® score in the low risk range, defined as an ROR of 40 or lower

 -  Subject has not yet initiated endocrine therapy

 -  Subject has signed study informed consent form

 Exclusion Criteria:

 • Does not meet every inclusion criteria listed above