Camizestrant

TTNT is defined as time from the date of the first administration of study treatment to the earliest start date of subsequent anti-cancer medication or death. The primary measure of interest is the TTNT event-free rate at 2 years.

IBCFS is defined as time from randomisation until date of first occurrence of: * Invasive ipsilateral breast tumour recurrence * Locoregional invasive breast cancer recurrence * Distant recurrence * Contralateral invasive breast cancer * Death attributable to any cause.

PFS is defined as the time from randomization to objective disease progression (as assessed by RECIST 1.1) or death.

PFS is defined as the time from randomization to objective disease progression (as assessed by RECIST) or death.

To investigate the safety and tolerability of camizestrant in combination with atirmociclib.

The pharmacodynamic (PD) effect of AZD9833 on ER expression comparing pre- and on-treatment tumour samples in women with early breast cancer after 5 to 7 days and 12 to 15 days of AZD9833 treatment was assessed. The assessment was done by immunohistochemistry (IHC) method. The percentage change was calculated from an analysis of covariance (ANCVOA) model adjusting for baseline ER score and day of on-treatment biopsy.

The PD effect of AZD9833 on ER expression comparing pre- and on-treatment tumour samples in women with early breast cancer after 5 to 7 days and 12 to 15 days of AZD9833 treatment was assessed. The assessment was done by IHC method. The sensitivity analysis excluded any patients who were HER2-positive patient by central assessment as well as patients with baseline ER H-score \< 10. The percentage change was calculated from ANCVOA model adjusting for baseline ER score and day of on-treatment biopsy.

PFS was assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST) version 1.1. PFS was defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or received another anti-cancer therapy prior to progression. Disease progression was defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions. Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable.

Cmax: maximum concentration

tmax : time to maximum concentration

area under the concentration-time curve (AUC) from zero to the last measurable concentration (AUClast)

area under the concentration-time curve (AUC) from zero to infinity (AUCinf)

tlast: time of the last measurable concentration

t1/2λz: apparent terminal elimination half-life

CL/F: apparent clearance;

Vz/F: apparent volume of distribution.

Assessment of the total radioactivity by measuring the cumulative amount of AZD9833 excreted

Assessment of the total radioactivity, expressed as a percentage, by measuring the cumulative amount of AZD9833 excreted

Dose-limiting toxicity as described in the protocol that is not related to disease progression, intercurrent illness or concomitant medications and that, despite optimal therapeutic intervention, meets protocol-defined criteria of AZD9833 monotherapy. \[part A only\]

Data will include clinical observations, ECG parameters, clinical chemistry and haematology and vital signs assessed as the number of subjects with treatment-related adverse events assessed by CTCAE v5.0 of AZD9833 monotherapy.

To characterise the single- and multiple-dose PK of AZD9833 monotherapy.

Data will include clinical observations, ECG parameters, clinical chemistry and haematology and vital signs assessed as the number of subjects with treatment-related adverse events assessed by CTCAE v4.03.