Lung Cancer in Women: The Past, Present, and Future.

Lung cancer is the leading cause of cancer death for women in multiple countries including the United States. Women are exposed to unique risk factors that remain largely understudied such as indoor pollution, second-hand tobacco exposure, biological differences, gender differences in tolerability and response to therapy in lung cancer, and societal gender roles, that create distinct survivorship needs. Women continue to lack representation in lung cancer clinical trials and are typically treated with data generated from majority male patient study populations, which may be inappropriate to extrapolate and generalize to females. Current lung cancer treatment and screening guidelines do not incorporate sex-specific differences and physicians also often do not account for gender differences when choosing treatments or discussing survivorship needs. To best provide targeted treatment approaches, greater representation of women in lung cancer clinical trials and further research is necessary. Clinicians should understand the unique factors and consequences associated with lung cancer in women; thus, a holistic approach that acknowledges environmental and societal factors is necessary.

Breast cancer treatment receipt and the role of financial stress, health literacy, and numeracy among diverse breast cancer survivors.

PURPOSE: Disparities in breast cancer treatment for low-income and minority women are well documented. We examined economic hardship, health literacy, and numeracy and whether these factors were associated with differences in receipt of recommended treatment among breast cancer survivors. METHODS: During 2018-2020, we surveyed adult women diagnosed with stage I-III breast cancer between 2013 and 2017 and received care at three centers in Boston and New York. We inquired about treatment receipt and treatment decision-making. We used Chi-squared and Fisher's exact tests to examine associations between financial strain, health literacy, numeracy (using validated measures), and treatment receipt by race and ethnicity. RESULTS: The 296 participants studied were 60.1% Non-Hispanic (NH) White, 25.0% NH Black, and 14.9% Hispanic; NH Black and Hispanic women had lower health literacy and numeracy and reported more financial concerns. Overall, 21 (7.1%) women declined at least one component of recommended therapy, without differences by race and ethnicity. Those not initiating recommended treatment(s) reported more worry about paying large medical bills (52.4% vs. 27.1%), worse household finances since diagnosis (42.9% vs. 22.2%), and more uninsurance before diagnosis (9.5% vs. 1.5%); all P < .05. No differences in treatment receipt by health literacy or numeracy were observed. CONCLUSION: In this diverse population of breast cancer survivors, rates of treatment initiation were high. Worry about paying medical bills and financial strain were frequent, especially among non-White participants. Although we observed associations of financial strain with treatment initiation, because few women declined treatments, understanding the scope of impact is limited. Our results highlight the importance of assessments of resource needs and allocation of support for breast cancer survivors. Novelty of this work includes the granular measures of financial strain and inclusion of health literacy and numeracy.

Breast cancer knowledge and understanding treatment rationales among diverse breast cancer survivors.

PURPOSE: The degree to which breast cancer survivors know about their tumors and understand treatment rationales is not well understood. We sought to identify information gaps within a diverse sample and explore whether knowledge about breast cancer and treatment may impact care. METHODS: We conducted a one-time, interviewer-administered survey of women who were diagnosed with breast cancer during 2013-2017 and received care at one of three centers in Boston, MA, and New York, NY. We examined knowledge of breast cancer and treatment rationales, information preferences, and treatment receipt. RESULTS: During 2018-2020, we interviewed 313 women (American Association for Public Opinion Research Cooperation Rates 58.4-76.5% across centers) who were 56.9% White, 23.6% Black, 14.1% Hispanic, and 5.4% other. Among the 296 included in analyses, we observed high variability in knowledge of breast cancer and treatment rationales, with a substantial number demonstrating limited knowledge despite feeling highly informed; > 25% actively avoided information. Black and Hispanic (vs. White) women consistently knew less about their cancers. Lack of understanding of treatment rationales for chemotherapy, radiation, and hormonal therapy was common but not consistently different by race and ethnicity. Understanding treatment rationale (but not cancer knowledge) was associated with treatment initiation, but small sample sizes limited in-depth examination. CONCLUSIONS: Our study highlights the need for enhanced informational support for breast cancer survivors, who are challenged with complex information during the decision-making process and beyond. More research is needed to understand how to further educate and empower diverse populations of patients with breast cancer.

Defining the patient experience in medical oncology.

PURPOSE: Higher patient satisfaction is associated with improved health outcomes, treatment adherence, and quality of life. The goal of this study was to explore oncology patients' perceptions on their hospital experience, focusing on the quality of care in medical oncology. METHODS: A qualitative and quantitative study design was implemented with a sample of 58 patients at Smilow Yale New Haven Hospital. Data were collected from patient interviews and observation of rounds. RESULTS: Two themes emerged: hospital experience and physician communication skills. Within hospital experience, subthemes identified include: attended to (49%), facility/staff (35%), nurses (33%), long wait time (29%), doctors (20%), coordination of care (18%), unnecessary medical procedures (10%), medications (6%), night awakenings (4%), pain (4%), not getting better (4%), and decreased mobility (2%). Within physician communication skills, subthemes identified include: involving the patient and/or family in the care process (41%), method of information sharing (18%), lack of coordination of care (15%), use of medical jargon (10%), attending to patient's needs (8%), and lack of patient's perspective (8%). Patients reported that effective engagement of patients in the care process and attending to patient-specific needs were desired qualities in their hospital experience as well as patient-centered communication with their physician. The quantitative data supported qualitative results with 72% of patients giving the highest score in overall satisfaction with their patient experience. CONCLUSION: Physician attentiveness or lack thereof is a defining aspect of the quality of patient experience and physician communication. The results are intended to inform clinical and operational interventions that care providers might incorporate into practice.

LEF1 is preferentially expressed in the tubal-peritoneal junctions and is a reliable marker of tubal intraepithelial lesions.

Recently it has been reported that serous tubal intraepithelial carcinoma (STIC), the likely precursor of ovarian/extra-uterine high-grade serous carcinoma, are frequently located in the vicinity of tubal-peritoneal junctions, consistent with the cancer-prone features of many epithelial transitional regions. To test if p53 (aka TP53)-signatures and secretory cell outgrowths (SCOUTs) also localize to tubal-peritoneal junctions, we examined these lesions in the fallopian tubes of patients undergoing salpingo-oophorectomy for sporadic high-grade serous carcinomas or as a prophylactic procedure for carriers of familial BRCA1 or 2 mutations. STICs were located closest to the tubal-peritoneal junctions with an average distance of 1.31 mm, while SCOUTs were not detected in the fimbriated end of the fallopian tube. As many epithelial transitional regions contain stem cells, we also determined the expression of stem cell markers in the normal fallopian tube, tubal intraepithelial lesions and high-grade serous carcinomas. Of those, LEF1 was consistently expressed in the tubal-peritoneal junctions and all lesions, independent of p53 status. All SCOUTs demonstrated strong nuclear expression of ß-catenin consistent with the LEF1 participation in the canonical WNT pathway. However, ß-catenin was preferentially located in the cytoplasm of cells comprising STICs and p53 signatures, suggesting WNT-independent function of LEF1 in those lesions. Both frequency of LEF1 expression and ß-catenin nuclear expression correlated with the worst 5-year patient survival, supporting important role of both proteins in high-grade serous carcinoma. Taken together, our findings suggest the existence of stem cell niche within the tubal-peritoneal junctions. Furthermore, they support the notion that the pathogenesis of SCOUTs is distinct from that of STICs and p53 signatures. The location and discrete patterns of LEF1 and ß-catenin expression may serve as highly sensitive and reliable ancillary markers for the detection and differential diagnosis of tubal intraepithelial lesions.

RANKL/RANK control Brca1 mutation- .

Breast cancer is the most common female cancer, affecting approximately one in eight women during their life-time. Besides environmental triggers and hormones, inherited mutations in the breast cancer 1 (BRCA1) or BRCA2 genes markedly increase the risk for the development of breast cancer. Here, using two different mouse models, we show that genetic inactivation of the key osteoclast differentiation factor RANK in the mammary epithelium markedly delayed onset, reduced incidence, and attenuated progression of Brca1;p53 mutation-driven mammary cancer. Long-term pharmacological inhibition of the RANK ligand RANKL in mice abolished the occurrence of Brca1 mutation-driven pre-neoplastic lesions. Mechanistically, genetic inactivation of Rank or RANKL/RANK blockade impaired proliferation and expansion of both murine Brca1;p53 mutant mammary stem cells and mammary progenitors from human BRCA1 mutation carriers. In addition, genome variations within the RANK locus were significantly associated with risk of developing breast cancer in women with BRCA1 mutations. Thus, RANKL/RANK control progenitor cell expansion and tumorigenesis in inherited breast cancer. These results present a viable strategy for the possible prevention of breast cancer in BRCA1 mutant patients.

Role of the stem cell niche in the pathogenesis of epithelial ovarian cancers.

Ovarian cancer is the fifth leading cause of cancer-related deaths among women in the United States. Recent extensive genomic analyses of epithelial ovarian cancer (EOC), particularly the most common and deadly form of high-grade serous ovarian carcinoma, have provided important insights into the repertoire of molecular aberrations that are characteristic for this malignancy. However, interpretation of the discovered aberrations is complicated because the origin and mechanisms of progression of EOC remain uncertain. Here, we summarize current views on the cell of origin of EOC and discuss recent findings of a cancer-prone stem cell niche for ovarian surface epithelium, one of the major likely sources of EOC. We also outline future directions and challenges in studying the role of stem cell niches in EOC pathogenesis.