...I ignored those who told me I was too opinionated and pushed back when I was encouraged to focus my surgery practice solely on taking care of women with breast cancer. Important and unprecedented ...progress has been made in cancer research in just the past three decades in the USA, with cancer mortality declining by a third in that timeframe.4 Yet, women still face unique gender-based barriers and challenges when interacting with cancer as patients, caregivers, researchers, or health-care providers.5–10 Achieving gender equality in the context of cancer research and care will require broad implementation of the recommendations in The Lancet Commission on women, power, and cancer, including the overarching priority action that sex and gender be included in all cancer-related policies and guidelines so that they are responsive to the needs and aspirations of women in all of their diversities. The oncology community, together with all of society, needs to harness the tremendous value that women bring to developing and implementing cancer policy, leading and conducting research, providing care, and engaging communities.
Connecting lab, clinic, and community Bertagnolli, Monica M.
Science (American Association for the Advancement of Science),
06/2024, Letnik:
384, Številka:
6700
Journal Article
Recenzirano
Odprti dostop
Despite great progress in biomedical research, the health of the US population appears to be getting worse. The United States spends substantially more per capita on health care than other wealthy ...countries, yet US life expectancy ranks low among its peers. Mortality rates have been increasing for segments of the US population, including those in rural areas, certain racial and ethnic groups, and individuals with low socioeconomic status. A whole-of-society approach is required to address such negative trends and disparities, and the biomedical research enterprise must play a key role.
Older adults with cancer are underrepresented in clinical research. Because of insufficient data, such patients and their physicians must make life-altering treatment decisions without adequate ...evidence-based guidance.
Molecular Basis of Colorectal Cancer Markowitz, Sanford D; Bertagnolli, Monica M
The New England journal of medicine,
12/2009, Letnik:
361, Številka:
25
Journal Article
Recenzirano
Odprti dostop
This review gives an account of recent advances in our knowledge of the molecular mechanisms in colorectal cancer. Genetic changes in the germ line, combined with somatic mutations, occur in familial ...syndromes of colorectal cancer, whereas somatic mutations are the outstanding feature of sporadic colorectal cancer. Genetic changes drive the progression from adenoma to carcinoma and probably influence individual susceptibility and response to treatment.
This review gives an account of recent advances in our knowledge of the molecular mechanisms of colorectal cancer. Genetic changes in the germ line, combined with somatic mutations, occur in familial syndromes of colorectal cancer, whereas somatic mutations are the outstanding feature of sporadic colorectal cancer.
Every year in the United States, 160,000 cases of colorectal cancer are diagnosed, and 57,000 patients die of the disease, making it the second leading cause of death from cancer among adults.
1
The disease begins as a benign adenomatous polyp, which develops into an advanced adenoma with high-grade dysplasia and then progresses to an invasive cancer.
2
Invasive cancers that are confined within the wall of the colon (tumor–node–metastasis stages I and II) are curable, but if untreated, they spread to regional lymph nodes (stage III) and then metastasize to distant sites (stage IV).
3
–
5
Stage I and II tumors are . . .
Over the past three decades, researchers in the NCI-funded cancer cooperative groups have routinely incorporated collection of biospecimens, quality of life assessments, diet and physical activity ...data and other health outcome variables from clinical trial participants to provide an expanding resource for correlative science in cancer clinical research.
Background
The prognosis for gastric cancer is better for Asian than for Caucasian patients. The primary driver of this difference is unknown. This study determined whether the survival advantage of ...Asian ethnicity continued to hold after control was used for other well-known prognostic factors.
Methods
In this study, 12,773 patients who underwent gastrectomy for treatment of adenocarcinoma of the stomach were identified from the Surveillance, Epidemiology, and End Results cancer registry. Patients with cardia tumor were excluded from the study. The independent prognostic effect of ethnicity was evaluated by adjusting for other known factors.
Results
The Asian patients tended to have a diagnosis at an earlier age (66.8 vs. 68.5 years), more lymph nodes examined (16 vs. 13), and more positive lymph nodes (5.1 vs. 4.8). Survival was better for the Asian patients than for the Caucasian patients, with a 12 % 5-year survival difference. Among the patients with IB, IIA, and IIB disease, the Asian patients had 37, 72, and 13 months longer median survival time than the corresponding Caucasian patients. The multivariate Cox model showed persistence of this result after adjustment for imbalances of age, gender, tumor grade, and number of examined and positive lymph nodes. The largest risk reduction was observed for the stage IA patients (31 %) and the smallest for the stage IIIC patients (9 %).
Conclusion
After excluding proximal gastric cancers, controlling for the imbalance of known prognostic factors, and decreasing in the influence of D2 lymphadenectomy, stage migration, and chemo/radiation therapy by including only patients treated in the United States, this study found that the survival advantage of Asian ethnicity continued to be present.
CALGB/SWOG 80405 was a randomized phase III trial that found no statistically significant difference in overall survival (OS) in patients with first-line metastatic colorectal cancer treated with ...chemotherapy plus either bevacizumab or cetuximab. Primary tumor DNA from 843 patients has been used to discover genetic markers of OS.
Gene mutations were determined by polymerase chain reaction. Microsatellite status was determined by genotyping of microsatellites. Tumor mutational burden (TMB) was determined by next-generation sequencing. Cox proportional hazard models were used, with adjusting factors. Interaction of molecular alterations with either the bevacizumab or the cetuximab arms was tested.
Patients with high TMB in their tumors had longer OS than did patients with low TMB (hazard ratio HR, 0.73 95% CI, 0.57 to 0.95;
= .02). In patients with microsatellite instability-high (MSI-H) tumors, longer OS was observed in the bevacizumab arm than in the cetuximab arm (HR, 0.13 95% CI, 0.06 to 0.30; interaction
< .001 for interaction between microsatellite status and the two arms). Patients with
mutant tumors had shorter OS than did patients with wild-type (WT) tumors (HR, 2.01 95% CI, 1.49 to 2.71;
< .001). Patients with extended
mutant tumors had shorter OS than did patients with WT tumors (HR, 1.52 95% CI, 1.26 to 1.84;
< .001). Patients with triple-negative tumors (WT for
/
/
) had a median OS of 35.9 months (95% CI, 33.0 to 38.8 months) versus 22.2 months (95% CI, 19.6 to 24.4 months ) in patients with at least one mutated gene in their tumors (
< .001).
In patients with metastatic colorectal cancer treated in first line, low TMB, and
and
mutations are negative prognostic factors. Patients with MSI-H tumors benefited more from bevacizumab than from cetuximab, and studies to confirm this effect of MSI-H are warranted.
To determine the predictive and prognostic value of the consensus molecular subtypes (CMSs) of colorectal cancer (CRC) that represent a merging of gene expression-based features largely in primary ...tumors from six independent classification systems and provide a framework for capturing the intrinsic heterogeneity of CRC in patients enrolled in CALGB/SWOG 80405.
CALGB/SWOG 80405 is a phase III trial that compared the addition of bevacizumab or cetuximab to infusional fluorouracil, leucovorin, and oxaliplatin or fluorouracil, leucovorin, and irinotecan as first-line treatment of advanced CRC. We characterized the CMS classification using a novel NanoString gene expression panel on primary CRCs from 581 patients enrolled in this study to assess the prognostic and predictive value of CMSs in these patients.
The CMSs are highly prognostic for overall survival (OS;
< .001) and progression-free survival (PFS;
< .001). Furthermore, CMSs were predictive for both OS (
for interaction < .001) and PFS (
for interaction = .0032). In the CMS1 cohort, patients treated with bevacizumab had a significantly longer OS than those treated with cetuximab (
< .001). In the CMS2 cohort, patients treated with cetuximab had a significantly longer OS than patients treated with bevacizumab (
= .0046).
These findings highlight the possible clinical utility of CMSs and suggests that refinement of the CMS classification may provide a path toward identifying patients with metastatic CRC who are most likely to benefit from specific targeted therapy as part of the initial treatment.
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