Frequent upregulation of HER2 protein in hormone-receptor-positive HER2-negative breast cancer after short-term neoadjuvant endocrine therapy.

BACKGROUND: Endocrine resistant metastatic disease develops in ~ 20-25% of hormone-receptor-positive (HR+) breast cancer (BC) patients despite endocrine therapy (ET) use. Upregulation of HER family receptor tyrosine kinases (RTKs) represent escape mechanisms in response to ET in some HR+ tumors. Short-term neoadjuvant ET (NET) offers the opportunity to identify early endocrine escape mechanisms initiated in individual tumors. METHODS: This was a single arm, interventional phase II clinical trial evaluating 4 weeks (± 1 week) of NET in patients with early-stage HR+/HER2-negative (HER2-) BC. The primary objective was to assess NET-induced changes in HER1-4 proteins by immunohistochemistry (IHC) score. Protein upregulation was defined as an increase of ≥ 1 in IHC score following NET. RESULTS: Thirty-seven patients with cT1-T3, cN0, HR+/HER2- BC were enrolled. In 35 patients with evaluable tumor HER protein after NET, HER2 was upregulated in 48.6% (17/35; p = 0.025), with HER2-positive status (IHC 3+ or FISH-amplified) detected in three patients at surgery, who were recommended adjuvant trastuzumab-based therapy. Downregulation of HER3 and/or HER4 protein was detected in 54.2% of tumors, whereas HER1 protein remained low and unchanged in all cases. While no significant volumetric reduction was detected radiographically after short-term NET, significant reduction in tumor proliferation rates were observed. No significant associations were identified between any clinicopathologic covariates and changes in HER1-4 protein expression on multivariable analysis. CONCLUSION: Short-term NET frequently and preferentially upregulates HER2 over other HER family RTKs in early-stage HR+/HER2- BC and may be a promising strategy to identify tumors that utilize HER2 as an early endocrine escape pathway. CLINICAL TRIAL REGISTRY: Trial registration number: NCT03219476.

Practice policy and quality initiatives: using lean principles to improve screening mammography workflow.

The "lean" approach is a quality improvement method that focuses on maximizing activities that are valued by the customer and eliminating waste that impedes efficiency in the workplace. The unique philosophy of the lean approach encourages all members of the team to be directly involved in identifying areas of waste and generating solutions to eliminate them. When the breast imaging section at the authors' institution became part of a multispecialty breast care center, the result was escalating examination volumes, more complex cases, and overall increased demand on radiologists' time. After several unsuccessful attempts to improve the efficiency of the section, including evaluation by outside consultants, the decision was made to embark on a comprehensive quality improvement program using the lean approach. A team of radiologists, technologists, file room personnel, information technology (IT) representatives, and administrators from the breast imaging section met twice a month to learn about lean principles and how to apply them to screening mammography workflows. Sources of inefficiency (waste) were identified, and potential solutions were generated. Multiple trials were performed to test these solutions. Throughout the process, all team members were engaged in identifying the problems, suggesting solutions, and implementing change. Most of the tested solutions were successful and resulted in decreased patient wait times, improved efficiency for the technologists and radiologists, faster report turnaround, and advances in IT. In addition, staff members were introduced to the lean philosophy and became actively involved in improving their workplace, resulting in a more cohesive section.

Missed Breast Cancer: What Can We Learn?

Multiple studies have shown that screening mammography helps to reduce mortality and morbidity from advanced breast cancer. However mammography does have its own limitations, and unfortunately, there are a fair number of false-negative mammograms. We are all aware that the sensitivity of mammography is inversely proportional to the breast density. With many states passing mandatory breast density reporting legislation, there has been an emphasis on using additional and alternative screening methods such as whole breast ultrasound and screening magnetic resonance imaging. Many cancers are simply not detected on mammography, even in retrospect. However, many of the breast cancers are actually visible retrospectively on the prior mammogram. It is these small and often subtle cancers that are perceptible but often missed, that provide a valuable learning opportunity. Studying the imaging findings of cancers that went undetected is a good learning exercise for the radiologist to identify common patterns and mistakes that lead to a missed cancer. This allows the radiologist to improve mammographic sensitivity and overall diagnostic accuracy. This article discusses some of the limitations of mammography, common sources of error which may lead to an undetected cancer, and also discuss a few pearls to prevent these common errors.

CT for thromboembolic disease.

CTPA has dramatically changed the diagnostic approach to PE in the last decade. The addition of CTV has created a single diagnostic test that can evaluate for both important components of venous thromboembolic disease. Newer, multislice scanners will provide thinner images and more complete anatomic coverage. Shorter scan times will minimize motion artifacts. These improvements may continue to improve the diagnostic yield of CTPA. The availability of an accurate noninvasive diagnostic tool to evaluate for PE and DVT should lead to a better understanding of the wide range of presentations of thromboembolic disease. The next decade may produce improvements in understanding of the epidemiology of PE and perhaps to a more tailored approach to treatment for thromboembolic disease.

Giant apocrine hidradenoma of the breast.

We report a case of a 26-year-old woman with an 8.0-cm tumor of the left breast. The tumor was clinically and radiologically suspicious for malignancy. The pathologic evaluation of the core biopsy and the subsequent excision specimen revealed a benign sclerosing, cystic, and papillary adnexal tumor with apocrine and clear cell morphology. The immunohistochemical staining for p63 was positive. Estrogen, progesterone, and Her-2 receptor immunohistochemical stains were negative. The cytogenetic analysis revealed 46, XX t(11:19) (q21;q13.1) balanced translocation. The final diagnosis was apocrine hidradenoma.