Incidence and prognostic impact of HER2-positivity loss after dual HER2-directed neoadjuvant therapy for HER2+ breast cancer.

BACKGROUND: Loss of HER2 "positivity" can occur in patients with residual disease after neoadjuvant treatment, but the incidence of HER2-positivity loss after neoadjuvant dual HER2-targeted treatment plus chemotherapy, the current standard-of-care for most early stage HER2-positive breast cancers, is not well described. Previous studies that report the HER2 discordance rate after neoadjuvant treatment also do not include the novel HER2-low category. In this retrospective study, we determine the incidence and prognostic impact of HER2-positivity loss, including the evolution to HER2-low disease, after neoadjuvant dual HER2-targeted therapy with chemotherapy. METHODS: Clinicopathologic data for patients with stage I-III HER2+ breast cancer diagnosed between 2015 and 2019 were reviewed in this single institution retrospective study. Patients who received dual HER2-targeted treatment with chemotherapy were included, and HER2 status before and after neoadjuvant therapy was interrogated. RESULTS: A total of 163 female patients were included in the analysis with a median age of 50 years. A pathologic complete response (pCR as defined by ypT0/is) was achieved in 102 (62.5%) of 163 evaluable patients. Among the 61 patients with residual disease after neoadjuvant therapy, 36 (59.0%) had HER2-positive and 25 (41.0%) had HER2-negative residual disease. Of the 25 patients with HER2-negative residual disease, 22 (88%) of patients were classified as HER2-low. After a median follow-up of 3.3 years, patients who retained HER2-positivity after neoadjuvant treatment had a 3-year IDFS rate of 91% (95% CI, 91%-100%), while patients who lost HER2-positivity had a 3-year IDFS rate of 82% (95% CI, 67%-100%). CONCLUSION: Almost half of patients with residual disease following neoadjuvant dual HER2-targeted therapy plus chemotherapy lost HER2-positivity. The loss of HER2-positivity may not confer negative prognostic impact, although the results were limited by short follow-up time. Further research on the HER2 status after neoadjuvant treatment may help guide treatment decisions in the adjuvant setting.

Supporting Volunteer Firefighter Well-Being: Lessons from the Australian "Black Summer" Bushfires.

INTRODUCTION: The 2019-2020 "Black Summer" bushfires in Australia focused the attention of the nation on the critical role that volunteer firefighters play in the response to such a disaster, spurring a national conversation about how to best support those on the frontline. The objective of this research was to explore the impact of the Black Summer bushfires on volunteer firefighter well-being and to investigate how to deliver effective well-being support. METHODS: An explorative qualitative design underpinned by a phenomenological approach was applied. Participant recruitment followed a multi-modal sampling strategy and data were collected through semi-structured, in-depth interviews. RESULTS: Qualitative data were collected from 58 participants aged from 23 to 61-years-of-age (average age of 46 years). All self-reported as volunteer firefighters who had responded to the Black Summer bushfires in Australia. Just over 80% of participants were male and the majority lived in the Australian states of New South Wales (65%) and Victoria (32%). All participants reported impact on their well-being, resulting from cumulative trauma exposure, responding to fires in local communities, intense work demands, minimal intervals between deployments, and disruption to primary employment. In regard to supporting well-being, four key themes emerged from data analysis: (1) Well-being support needs to be both proactive and reactive and empower local leaders to "reach in" while encouraging responders to "reach out;" (2) Employee Assistance Programs (EAPs) should not be the only well-being support option available; (3) The sharing of lived experience is important; and (4) Support programs need to address self-stigmatization. CONCLUSION: Participants in this research identified that effective well-being support needs to be both proactive and reactive and holistic in approach.

Health Trends among 9/11 Responders from 2011-2021: A Review of World Trade Center Health Program Statistics.

INTRODUCTION: In a single day, the September 11, 2001 US terrorist attacks (9/11) killed nearly 3,000 people, including 412 first responders. More than 91,000 responders were exposed to a range of hazards during the recovery and clean-up operation that followed. Various health programs track the on-going health effects of 9/11, including the World Trade Center (WTC) Health Program (WTCHP). The objective of this research was to review WTCHP statistics reported by the Centers for Disease Control and Prevention (CDC) to analyze health trends among enrolled responders as the 20-year anniversary of the terrorist attacks approaches. METHODS: The WTCHP statistics reported by the CDC were analyzed to identify health trends among enrolled responders from 2011 through 2021. Statistics for non-responders were excluded. RESULTS: A total of 80,745 responders were enrolled in the WTCHP as of March 2021: 62,773 were classified as general responders; 17,023 were Fire Department of New York (FDNY) responders; and 989 were Pentagon and Shanksville responders. Of the total responders in the program, 3,439 are now deceased. Just under 40% of responders with certified health issues were aged 45-64 and 83% were male. The top three certified conditions among enrolled responders were: aerodigestive disorders; cancer; and mental ill health. The top ten certified cancers have remained the same over the last five years, however, leukemia has now overtaken colon and bladder cancer as the 20-year anniversary approaches. Compared to the general population, 9/11 first responders had a higher rate of all cancers combined, as well as higher rates of prostate cancer, thyroid cancer, and leukemia. DISCUSSION: Trends in these program statistics should be viewed with some caution. While certain illnesses have been linked with exposure to the WTC site, differences in age, sex, ethnicity, smoking status, and other factors between exposed and unexposed groups should also be considered. Increased rates of some illnesses among this cohort may be associated with heightened surveillance rather than an actual increase in disease. Still, cancer in general, as well as lung disease, heart disease, and posttraumatic stress disorder (PTSD), seem to be increasing among 9/11 responders, even now close to 20 years later. CONCLUSION: Responders should continue to avail themselves of the health care and monitoring offered through programs like the WTCHP.