Divergent Cellular Expression Patterns of PD-L1 and PD-L2 Proteins in Breast Cancer.

PD-L1 immunohistochemistry (IHC) has become an established method for predicting cancer response to targeted anti-PD1 immunotherapies, including breast cancer (BC). The alternative PD-1 ligand, PD-L2, remains understudied but may be a complementary predictive marker. Prospective analysis of 32 breast cancers revealed divergent expression patterns of PD-L1 and PD-L2. PD-L1-positivity was higher in immune cells than in cancer cells (median = 5.0% vs. 0.0%; p = 0.001), whereas PD-L2-positivity was higher in cancer cells than immune cells (median = 30% vs. 5.0%; p = 0.001). Percent positivity of PD-L1 and PD-L2 were not correlated, neither in cancer cells nor immune cells. Based on a cut-point of ≥1% positivity, ER+ tumors (n = 23) were frequently PD-L2-positive (73.9%), whereas only 40.9% were PD-L1-positive. These data suggest differential control of cellular PD-L1 and PD-L2 expression in BC and a potential role for PD-L2 IHC as a complementary marker to PD-L1 to improve selection of aggressive ER+ BC that may benefit from anti-PD-1 therapy.

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.

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. Trial registration number: NCT03219476 Date of registration for prospectively registered trials: July 17, 2017.

Medical students and mattering on the surgery clerkship rotation.

BACKGROUND: Mattering is a psychosocial construct that describes an individual's perception that they make a difference in the lives of others and that they are significant in the world. The purpose of this study was to explore the current perception of behaviors that impact mattering among third year medical students on their surgery clerkship with the goal of improving the clerkship experience. METHODS: A qualitative interview study was conducted during the 2019-2020 academic year. Medical students who had completed their surgery clerkship at a single institution volunteered to participate. Qualitative thematic analysis of students' comments during interviews were categorized to the three primary domains of mattering: awareness, importance, and reliance. RESULTS: Six medical student interviews were conducted and responses were coded for the three primary domains of mattering. Eight subthemes emerged highlighting positive observations that may influence student mattering on the surgery clerkship. Awareness behaviors included acknowledging the student's presence, maintaining eye contact, educators offering students their undivided attention, and getting to know the students as individuals. Importance behaviors included taking time to teach, setting expectations early, and providing timely feedback. Reliance behaviors involve developing trust to match autonomy with experience and depending on students to provide unique information about patient care to the team. CONCLUSIONS: These findings can help educators recognize the words, actions, and behaviors that make medical students feel they matter on their surgery clerkship. Interventions should continue focus on how to increase the sense of awareness, importance, and reliance for both the students and faculty.

Breast Surgery Cost Savings Through Surgical Tray Instrument Reduction.

INTRODUCTION: Removing unnecessary instruments from surgical trays used in the operating room conserves resources and time. We aimed to assess the cost savings impact of breast surgical tray instrument reduction. METHODS: Breast surgeons at a single institution reviewed the standard surgical tray used for lumpectomies and mastectomies and removed underutilized instruments to create a breast-specific tray. This tray was used for all breast surgeries performed throughout the 2019 calendar year. Data for breast-specific tray usage, instrument reprocessing costs, and instrument maintenance costs for inspection, sharpening, aligning, and lubricating were retrospectively obtained. RESULTS: The breast-specific tray was reduced from 82 to 65 instruments. The cost of reprocessing each instrument is $1.69. After 30 tray sterilizations, each tray was sent for maintenance at a cost of $2.00 per instrument. With 10 breast-specific trays in circulation, the trays were used a total of 656 times during the calendar year. Each tray was sent for maintenance an average of two times during this time period. Thus, instrument reduction resulted in $18,847 in instrument reprocessing and $680.00 in maintenance savings, with total annual cost savings of $19,527. CONCLUSIONS: Optimizing surgical trays by removing unused instruments yields significant cost savings and contributes to improved efficiency in the sterile processing department. As efforts to eliminate wasteful practices and reduce costs within the health care system continue, opportunities remain for standardization of trays across all surgical departments and institutions.

Innovation in Breast Surgery: Practical and Ethical Considerations.

The adoption of innovation is essential to the evolution of patient care. Breast surgical oncology advances through incorporating new techniques, devices, and procedures. Historical changes in practice standards from radical to modified radical mastectomy or axillary node dissection to sentinel node biopsy reduced morbidity without sacrifice in oncologic outcome. Contemporary oncoplastic techniques afford broader consideration for breast conservation and the potential for improved cosmetic outcomes. At present, many breast surgeons face the decision of which wireless device to use for localization of nonpalpable lesions. Consideration for future changes, such as robotic mastectomy, are on the horizon. No guideline exists to assist breast surgeons in the adoption of innovation into practice. The Ethics Committee of the American Society of Breast Surgeons acknowledges that breast surgeons confront many questions associated with onboarding innovation. This paper aims to provide a framework for asking relevant questions along with the ethical principles to consider when integrating an innovation into practice.

Engaging young African American women breast cancer survivors: A novel storytelling approach to identify patient-centred research priorities.

BACKGROUND: Patient-centredness is considered an essential aspiration of a high-quality health-care system, and patient engagement is a critical precursor to patient-centred care. OBJECTIVES: To engage patients, health-care providers and stakeholders in identifying recommendations to address research and practice gaps that impact young African American breast cancer survivors. METHODS: This paper reported an approach for research priority setting. This approach applies an engagement process (January-September 2018) of using patient and stakeholder groups, patient storytelling workshops and a culminating storytelling conference in Wisconsin to generate relevant research topics and recommendations. Topics were prioritized using an iterative engagement process. Research priorities and recommendation were ranked over the conference by counting participants' anonymous votes. RESULTS: One hundred attendees (43 patients/family members, 20 providers/researchers and 37 community members) participated in the conference. Five topics were identified as priorities. The results showed that three priority areas received the most votes, specifically community outreach and education, providing affordable health care and engaging in complementary care practice. Stakeholders also agreed it is critical to 'include youth in the conversation' when planning for cancer support and educational programmes for caregivers, friends and family members. CONCLUSION: Storytelling as a patient engagement approach can build trust in the patient-research partnership, ensure that patients are meaningfully engaged throughout the process and capture the diversity of patient experiences and perspectives.

Management of the axilla after neo-adjuvant chemotherapy for breast cancer: Sentinel node biopsy and radiotherapy considerations.

Preoperative or neo-adjuvant chemotherapy in the management of breast cancer is a treatment approach that has gained in popularity in recent years. However, it is unclear if the treatment paradigms often employed for patients treated with surgery first hold true for those treated with preoperative chemotherapy. The role of sentinel node biopsy and the data supporting its use is different for those with clinically negative and clinically positive nodes prior to chemotherapy. For clinically node-negative patients, sentinel node biopsy after neo-adjuvant chemotherapy may be appropriate. For those node-positive patients whose axillary disease resolves clinically, the false-negative rate of the sentinel node biopsy is high. However, there are measures that can reduce that rate. After surgery, the radiation oncologist is often faced with complicated decisions surrounding the optimal radiotherapy in this setting. Tailoring radiation plans based on chemotherapy response holds promise and is the subject of ongoing clinical trials. In the accompanying article, we review the current literature on both surgery and radiation in axillary management and describe the interplay between these two treatment modalities. This highlights the need for multidisciplinary management in making treatment decisions for patients treated in this manner.

Ethical Considerations of Medical Photography in the Management of Breast Disease.

BACKGROUND: Medical photography has become an important component of the evaluation and management of patients across many specialties. It is increasingly utilized in contemporary practice with modern smartphones and enhanced digital media. Photography can enhance and improve treatment plans and communication between providers and patients. Additionally, photography supplements education, research, and marketing in both print and social media. Ethical and medicolegal standards for medical photography, specifically for patients with breast disease, have not been formally developed to guide medical providers. PURPOSE: To provide guidelines for breast care physicians using medical photography, the Ethics Committee of the American Society of Breast Surgeons presents an updated review of the literature and recommendations for ethical and practical use of photography in patient care. METHODS: An extensive PubMed review of articles in English was performed to identify studies and articles published prior to 2018 investigating the use of medical photography in patient care and the ethics of medical photography. After review of the literature, members of the Ethics Committee convened a panel discussion to identify best practices for the use of medical photography in the breast care setting. Results of the literature and panel discussion were then incorporated to provide the content of this article. CONCLUSION: The Ethics Committee of the American Society of Breast Surgeons acknowledges that photography of the breast has become an invaluable tool in the delivery of state-of-the-art care to our patients with breast disease, and we encourage the use of this important medium. Physicians must be well informed regarding the concerns associated with medical photography of the breast to optimize its safe and ethical use in clinical practice.

Changes in margin re-excision rates: Experience incorporating the "no ink on tumor" guideline into practice.

INTRODUCTION: Prior to the "no ink on tumor" SSO/ASTRO consensus guideline, approximately 20% of women with stage I/II breast cancers undergoing breast conservation surgery at our institution underwent margin re-excision. On May 20, 2013, our institution changed the definition of negative margins from 2 mm to "no ink on tumor." METHODS: A retrospective review was conducted of patients who had surgery at our institution with clinical stage I/II breast cancers between June 1, 2011 and May 1, 2015. In the pre-guideline cohort (pre) and post-guideline cohort (post), negative margins were 2 mm and "no ink on tumor," respectively. RESULTS: Implementation of the guideline resulted in a significant decrease in the positive/close margin rate (29.6% pre vs 10.1% post; P < 0.001) and numerical decrease in re-excision rate (20.4% pre vs 16.3% post; P = 0.104). No significant difference was found in local recurrence between the cohorts with limited follow-up (1.2% pre vs 1.5% post; P = 0.787). CONCLUSION: The implementation of the "no ink on tumor" guideline at our institution has resulted in a significant decrease in positive margin rates and a numerical decrease in margin re-excisions. In addition to margin status, surgeons continue to use individual patient and histologic factors to decide for or against margin re-excision.