Jane Macaskill

Phase II Randomized Preoperative Window-of-Opportunity Study of the PI3K Inhibitor Pictilisib Plus Anastrozole Compared With Anastrozole Alone in Patients With Estrogen Receptor–Positive Breast Cancer

PURPOSE Preclinical data support a key role for the PI3K pathway in estrogen receptor-positive breast cancer and suggest that combining PI3K inhibitors with endocrine therapy may overcome resistance. This preoperative window study assessed whether adding the PI3K inhibitor pictilisib (GDC-0941) can increase the antitumor effects of anastrozole in primary breast cancer and aimed to identify the most appropriate patient population for combination therapy. PATIENTS AND METHODS In this randomized, open-label phase II trial, postmenopausal women with newly diagnosed operable estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers were recruited. Participants were randomly allocated (2:1, favoring the combination) to 2 weeks of preoperative treatment with anastrozole 1 mg once per day (n = 26) or the combination of anastrozole 1 mg with pictilisib 260 mg once per day (n = 49). The primary end point was inhibition of tumor cell proliferation as measured by change in Ki-67 protein expression between tumor samples taken before and at the end of treatment. RESULTS There was significantly greater geometric mean Ki-67 suppression of 83.8% (one-sided 95% CI, ≥ 79.0%) for the combination and 66.0% (95% CI, ≤ 75.4%) for anastrozole (geometric mean ratio [combination:anastrozole], 0.48; 95% CI, ≤ 0.72; P = .004). PIK3CA mutations were not predictive of response to pictilisib, but there was significant interaction between response to treatment and molecular subtype (P = .03); for patients with luminal B tumors, the combination:anastrozole geometric mean ratio of Ki-67 suppression was 0.37 (95% CI, ≤ 0.67; P = .008), whereas no significant Ki-67 response was observed for pictilisib in luminal A tumors (1.01; P = .98). Multivariable analysis confirmed Ki-67 response to the combination treatment of patients with luminal B tumors irrespective of progesterone receptor status or baseline Ki-67 expression. CONCLUSION Adding pictilisib to anastrozole significantly increases suppression of tumor cell proliferation in luminal B primary breast cancer.

Volpara™ as a measurement tool for breast volume☆

Mammography has been a standard form of imaging the breast in the United Kingdom since 1988. With the advent of full-field digital mammography, software tools designed to provide automated breast density assessment are now available. These tools have emerged because mammographic breast density is an important risk factor for breast cancer. The two commercially available systems are Quantra (Hologic Inc., Bedford, MA, USA) and Volpara (Matakina, Wellington, New Zealand). They calculate breast volume and density based on area and thickness measurements derived from the raw versions of the two-view digital mammograms. The overall breast volume is then used as the denominator for the volumetric percentage of fibroglandular tissue. We aim to assess the validity of Volpara as a breast volume measurement tool by comparing Volpara volume measurements to actual skin sparing mastectomy (SSM) specimen volumes obtained intra-operatively. A prospective database of 43 SSM specimens in 39 women were analysed. Immediately following SSM, direct volume measurements were performed intra-operatively using a water displacement technique. The excised breast tissue was placed in a cylinder of water and the volume of displaced water measured. Intraoperative volumes were compared to the Volpara volumes using the Pearson’s coefficient test and intraclass correlation coefficient (ICC). Analysis was performed using SPSS v21 by the authors following advice from a trust statistician. The mean Volpara volume measurement was 660 cc (range 285e1270 cc) and the mean mastectomy volume measured intra-operatively 393 cc (range 50e900 cc). Pearson’s correlation test showed a statistically significant correlation of 0.81, p < 0.01 (R Z 0.657). ICC established moderate agreement with n Z 0.67 for mean values and n Z 0.51 for single measures, 95% CI. Breast density measurements in radiological investigations have been widely researched, with papers substantiating the correlation of density with the risk of malignancy. It is only in the last decade that interest in volume has grown. In breast conservation surgery, the ratio of parenchyma removed has been shown to greatly affect cosmetic outcome and patient satisfaction. In mastectomies, pre-operative knowledge of breast volume can guide the surgeon in estimating what is required to be replaced, either in the form of flaps, implants or a combination of both. There are many merits to using mammography to calculate breast volumes. It is almost invariable that any patient who undergoes a mastectomy for oncological

Identification of pathological complete response after neoadjuvant chemotherapy for breast cancer: comparison of greyscale ultrasound, shear wave elastography, and MRI

AIM To assess the value of post-treatment shear-wave elastography (SWE) parameters (maximum stiffness [Emax], mean stiffness [Emean], and standard deviation [SD]) compared to greyscale ultrasonography (US) and magnetic resonance imaging (MRI) in identifying pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) in breast cancer. MATERIALS AND METHODS In a prospective cohort study, 80 patients receiving NACT for breast cancer underwent baseline and post-treatment US, SWE, and MRI examinations. Four SWE images in two orthogonal planes were obtained. Maximum greyscale US diameter and maximum diameter of lesion enhancement on MRI were measured. Percentage reductions between baseline and post-treatment scans were calculated for MRI and greyscale US diameter, and Emean, Emax, and SD. The percentage reduction in Emean and US diameter were also analysed as a combination. Analysis was undertaken using receiver operating characteristic (ROC) curves and the chi-squared test. RESULTS pCR occurred in 21 of 80 (26%) women. The area under the ROC curve (AUC) for pCR of percentage reductions in Emean, Emax, SD, and greyscale US diameter were 0.89, 0.85, 0.75, and 0.86, respectively. The combination of percentage reductions in Emean and greyscale ultrasound diameter yielded an AUC of 0.92, which is similar to the AUC for MRI of 0.96 (p=0.28). CONCLUSIONS SWE combined with greyscale US shows promise for end-of-treatment identification of response to NACT in women with breast cancer, with accuracies similar to breast MRI. This technique could be used to inform surgical decision-making after NACT.