Breast Cancer ICYMI

A cohort study by Minami and colleagues assessed the association between surgery type (lumpectomy vs mastectomy) and change in frailty status in older patients with early-stage breast cancer (BC) undergoing locoregional therapy. The study included 31,084 women, age ≥ 65 years, with ductal carcinoma in situ (n = 9962) or stage I hormone receptor–positive (HR+) and ERBB2+ (human epidermal growth factor receptor 2 positive [HER2+]) BC (n = 21,122), of which 22.6% and 77.4% of patients underwent mastectomy and lumpectomy, respectively. The study showed that older patients who underwent mastectomy vs lumpectomy were more likely to experience worse frailty (adjusted odds ratio 1.31; 95% CI 1.23-1.39). Additionally, women who were robust vs having moderate to severe frailty at baseline, ≥ 75 years vs 65-69 years, or African American/Black vs non-Hispanic White, had significantly higher odds of decline. Given that prior data have shown comparable survival between lumpectomy and mastectomy, careful and thoughtful treatment considerations are needed before deciding to intensify surgical management in this population, even in women who do not appear frail at baseline.

Low-dose tamoxifen continues to prevent BC recurrence in breast noninvasive neoplasia

Low-dose tamoxifen is a treatment option for women with noninvasive BC, especially if the patient was not able to tolerate the standard dose of 20 mg daily. The phase 3 TAM-01 trial included 500 women with intraepithelial neoplasia of the breast who were randomly assigned to receive low-dose tamoxifen (5 mg once daily) or placebo. The 10-year follow-up analysis by Lazzeroni and colleagues showed that treatment with low-dose tamoxifen for 3 years continued to prevent a BC recurrence for at least 7 years after treatment cessation. After a median follow-up of 9.7 years, fewer cases of both invasive and in situ BC (hazard ratio 0.58; log-rank P = .03) and contralateral BC (hazard ratio 0.36; P = .025) were reported in the tamoxifen vs placebo group. These results are meaningful, especially in a setting of an optimal safety profile, where patients on low-dose tamoxifen were experiencing similar menopausal symptoms to placebo, and serious adverse events, such as deep vein thrombosis and pulmonary embolism, were not increased during low-dose tamoxifen therapy. This is different from the threefold increased risk reported with standard dosing.

Worse survival in BRCA1/2 germline mutation carriers receiving ET in HR+/HER2− BC

Inconsistent data have been reported on the prognostic impact of BRCA1/2 mutation in HR+ BC. A retrospective study by Frenel and colleagues included 13,776 patients with metastatic BC (MBC) from the Epidemiological Strategy and Medical Economics (ESME) MBC database, of which 676 and 170 patients were germline BRCA wild-type (gBRCAwt) and germline BRCA mutation (gBRCAm) carriers, respectively. They looked at outcomes and first-line endocrine treatment efficacy in patients with HR+/HER2- MBC, treated in a pre–cyclin-dependent kinase (CDK) 4/6 inhibitors era. The results showed that gBRCAm carriers had shorter overall survival (OS; adjusted hazard ratio [aHR] 1.26; P = .024) and progression-free survival (PFS; aHR 1.21; P = .017) compared with gBRCAwt carriers. Furthermore, among those treated with front-line endocrine therapy, gBRCAm patients had lower adjusted OS (aHR [95% CI] 1.54 [1.03-2.32]) and PFS (aHR [95% CI] 1.58 [1.17-2.12]) compared with gBRCAwt patients. Outcomes were similar for gBRCAm patients who received first-line chemotherapy compared with the gBRCAwt group (OS: aHR [95% CI] 1.12 [0.88-1.41]; first-line PFS: aHR [95% CI] 1.09 [0.90-1.31]). A previous retrospective study by Lambertini and colleagues, focusing on young patients with gBRCAm, also showed a tendency for a worse distant recurrence-free interval (aHR 1.39; 95% CI  0.94-2.05) in patients with HR+ BC. Additional studies are needed, especially in the setting of an evolving treatment landscape that includes CDK4/6 inhibitors and poly-ADP ribose polymerase (PARP) inhibitors.

A cohort study by Minami and colleagues assessed the association between surgery type (lumpectomy vs mastectomy) and change in frailty status in older patients with early-stage breast cancer (BC) undergoing locoregional therapy. The study included 31,084 women, age ≥ 65 years, with ductal carcinoma in situ (n = 9962) or stage I hormone receptor–positive (HR+) and ERBB2+ (human epidermal growth factor receptor 2 positive [HER2+]) BC (n = 21,122), of which 22.6% and 77.4% of patients underwent mastectomy and lumpectomy, respectively. The study showed that older patients who underwent mastectomy vs lumpectomy were more likely to experience worse frailty (adjusted odds ratio 1.31; 95% CI 1.23-1.39). Additionally, women who were robust vs having moderate to severe frailty at baseline, ≥ 75 years vs 65-69 years, or African American/Black vs non-Hispanic White, had significantly higher odds of decline. Given that prior data have shown comparable survival between lumpectomy and mastectomy, careful and thoughtful treatment considerations are needed before deciding to intensify surgical management in this population, even in women who do not appear frail at baseline.

Low-dose tamoxifen continues to prevent BC recurrence in breast noninvasive neoplasia

Low-dose tamoxifen is a treatment option for women with noninvasive BC, especially if the patient was not able to tolerate the standard dose of 20 mg daily. The phase 3 TAM-01 trial included 500 women with intraepithelial neoplasia of the breast who were randomly assigned to receive low-dose tamoxifen (5 mg once daily) or placebo. The 10-year follow-up analysis by Lazzeroni and colleagues showed that treatment with low-dose tamoxifen for 3 years continued to prevent a BC recurrence for at least 7 years after treatment cessation. After a median follow-up of 9.7 years, fewer cases of both invasive and in situ BC (hazard ratio 0.58; log-rank P = .03) and contralateral BC (hazard ratio 0.36; P = .025) were reported in the tamoxifen vs placebo group. These results are meaningful, especially in a setting of an optimal safety profile, where patients on low-dose tamoxifen were experiencing similar menopausal symptoms to placebo, and serious adverse events, such as deep vein thrombosis and pulmonary embolism, were not increased during low-dose tamoxifen therapy. This is different from the threefold increased risk reported with standard dosing.

Worse survival in BRCA1/2 germline mutation carriers receiving ET in HR+/HER2− BC

Inconsistent data have been reported on the prognostic impact of BRCA1/2 mutation in HR+ BC. A retrospective study by Frenel and colleagues included 13,776 patients with metastatic BC (MBC) from the Epidemiological Strategy and Medical Economics (ESME) MBC database, of which 676 and 170 patients were germline BRCA wild-type (gBRCAwt) and germline BRCA mutation (gBRCAm) carriers, respectively. They looked at outcomes and first-line endocrine treatment efficacy in patients with HR+/HER2- MBC, treated in a pre–cyclin-dependent kinase (CDK) 4/6 inhibitors era. The results showed that gBRCAm carriers had shorter overall survival (OS; adjusted hazard ratio [aHR] 1.26; P = .024) and progression-free survival (PFS; aHR 1.21; P = .017) compared with gBRCAwt carriers. Furthermore, among those treated with front-line endocrine therapy, gBRCAm patients had lower adjusted OS (aHR [95% CI] 1.54 [1.03-2.32]) and PFS (aHR [95% CI] 1.58 [1.17-2.12]) compared with gBRCAwt patients. Outcomes were similar for gBRCAm patients who received first-line chemotherapy compared with the gBRCAwt group (OS: aHR [95% CI] 1.12 [0.88-1.41]; first-line PFS: aHR [95% CI] 1.09 [0.90-1.31]). A previous retrospective study by Lambertini and colleagues, focusing on young patients with gBRCAm, also showed a tendency for a worse distant recurrence-free interval (aHR 1.39; 95% CI  0.94-2.05) in patients with HR+ BC. Additional studies are needed, especially in the setting of an evolving treatment landscape that includes CDK4/6 inhibitors and poly-ADP ribose polymerase (PARP) inhibitors.

A cohort study by Minami and colleagues assessed the association between surgery type (lumpectomy vs mastectomy) and change in frailty status in older patients with early-stage breast cancer (BC) undergoing locoregional therapy. The study included 31,084 women, age ≥ 65 years, with ductal carcinoma in situ (n = 9962) or stage I hormone receptor–positive (HR+) and ERBB2+ (human epidermal growth factor receptor 2 positive [HER2+]) BC (n = 21,122), of which 22.6% and 77.4% of patients underwent mastectomy and lumpectomy, respectively. The study showed that older patients who underwent mastectomy vs lumpectomy were more likely to experience worse frailty (adjusted odds ratio 1.31; 95% CI 1.23-1.39). Additionally, women who were robust vs having moderate to severe frailty at baseline, ≥ 75 years vs 65-69 years, or African American/Black vs non-Hispanic White, had significantly higher odds of decline. Given that prior data have shown comparable survival between lumpectomy and mastectomy, careful and thoughtful treatment considerations are needed before deciding to intensify surgical management in this population, even in women who do not appear frail at baseline.

Low-dose tamoxifen continues to prevent BC recurrence in breast noninvasive neoplasia

Low-dose tamoxifen is a treatment option for women with noninvasive BC, especially if the patient was not able to tolerate the standard dose of 20 mg daily. The phase 3 TAM-01 trial included 500 women with intraepithelial neoplasia of the breast who were randomly assigned to receive low-dose tamoxifen (5 mg once daily) or placebo. The 10-year follow-up analysis by Lazzeroni and colleagues showed that treatment with low-dose tamoxifen for 3 years continued to prevent a BC recurrence for at least 7 years after treatment cessation. After a median follow-up of 9.7 years, fewer cases of both invasive and in situ BC (hazard ratio 0.58; log-rank P = .03) and contralateral BC (hazard ratio 0.36; P = .025) were reported in the tamoxifen vs placebo group. These results are meaningful, especially in a setting of an optimal safety profile, where patients on low-dose tamoxifen were experiencing similar menopausal symptoms to placebo, and serious adverse events, such as deep vein thrombosis and pulmonary embolism, were not increased during low-dose tamoxifen therapy. This is different from the threefold increased risk reported with standard dosing.

Worse survival in BRCA1/2 germline mutation carriers receiving ET in HR+/HER2− BC

Inconsistent data have been reported on the prognostic impact of BRCA1/2 mutation in HR+ BC. A retrospective study by Frenel and colleagues included 13,776 patients with metastatic BC (MBC) from the Epidemiological Strategy and Medical Economics (ESME) MBC database, of which 676 and 170 patients were germline BRCA wild-type (gBRCAwt) and germline BRCA mutation (gBRCAm) carriers, respectively. They looked at outcomes and first-line endocrine treatment efficacy in patients with HR+/HER2- MBC, treated in a pre–cyclin-dependent kinase (CDK) 4/6 inhibitors era. The results showed that gBRCAm carriers had shorter overall survival (OS; adjusted hazard ratio [aHR] 1.26; P = .024) and progression-free survival (PFS; aHR 1.21; P = .017) compared with gBRCAwt carriers. Furthermore, among those treated with front-line endocrine therapy, gBRCAm patients had lower adjusted OS (aHR [95% CI] 1.54 [1.03-2.32]) and PFS (aHR [95% CI] 1.58 [1.17-2.12]) compared with gBRCAwt patients. Outcomes were similar for gBRCAm patients who received first-line chemotherapy compared with the gBRCAwt group (OS: aHR [95% CI] 1.12 [0.88-1.41]; first-line PFS: aHR [95% CI] 1.09 [0.90-1.31]). A previous retrospective study by Lambertini and colleagues, focusing on young patients with gBRCAm, also showed a tendency for a worse distant recurrence-free interval (aHR 1.39; 95% CI  0.94-2.05) in patients with HR+ BC. Additional studies are needed, especially in the setting of an evolving treatment landscape that includes CDK4/6 inhibitors and poly-ADP ribose polymerase (PARP) inhibitors.

A genetic sequencing effort identified more patients to be carriers of risk genes for hereditary breast and ovarian cancer or Lynch syndrome than would have been discovered by following existing genetic testing guidelines, according to new research.

The authors of the clinical trial suggest that these guidelines may need to be revised.

Individuals with hereditary breast and ovarian cancer (HBOC) have an 80% lifetime risk of breast cancer and are at greater risk of ovarian cancer, pancreatic cancer, prostate cancer, and melanoma. Those with Lynch syndrome (LS) have an 80% lifetime risk of colorectal cancer, a 60% lifetime risk of endometrial cancer, and heightened risk of upper gastrointestinal, urinary tract, skin, and other tumors, said study coauthor N. Jewel Samadder, MD in a statement.

The National Cancer Control Network has guidelines for determining family risk for colorectal cancer and breast, ovarian, and pancreatic cancer to identify individuals who should be screened for LS and HBOC, but these rely on personal and family health histories.

“These criteria were created at a time when genetic testing was cost prohibitive and thus aimed to identify those at the greatest chance of being a mutation carrier in the absence of population-wide whole-exome sequencing. However, [LS and HBOC] are poorly identified in current practice, and many patients are not aware of their cancer risk,” said Dr. Samadder, professor of medicine and coleader of the precision oncology program at the Mayo Clinic Comprehensive Cancer Center, Phoenix, in the statement.

Whole-exome sequencing covers only protein-coding regions of the genome, which is less than 2% of the total genome but includes more than 85% of known disease-related genetic variants, according to Emily Gay, who presented the trial results (Abstract 5768) on April 18 at the annual meeting of the American Association for Cancer Research.

“In recent years, the cost of whole-exome sequencing has been rapidly decreasing, allowing us to complete this test on saliva samples from thousands, if not tens of thousands of patients covering large populations and large health systems,” said Ms. Gay, a genetic counseling graduate student at the University of Arizona, during her presentation.

She described results from the TAPESTRY clinical trial, with 44,306 participants from Mayo Clinic centers in Arizona, Florida, and Minnesota, who were identified as definitely or likely to be harboring pathogenic mutations and consented to whole-exome sequencing from saliva samples. They used electronic health records to determine whether patients would satisfy the testing criteria from NCCN guidelines.

The researchers identified 1.24% of participants to be carriers of HBOC or LS. Of the HBOC carriers, 62.8% were female, and of the LS carriers, 62.6% were female. The percentages of HBOC and LS carriers who were White were 88.6 and 94.5, respectively. The median age of both groups was 57 years. Of HBOC carriers, 47.3% had personal histories of cancers; for LS carries, the percentage was 44.2.

Of HBOC carriers, 49.1% had been previously unaware of their genetic condition, while an even higher percentage of patients with LS – 59.3% – fell into that category. Thirty-two percent of those with HBOC and 56.2% of those with LS would not have qualified for screening using the relevant NCCN guidelines.

“Most strikingly,” 63.8% of individuals with mutations in the MSH6 gene and 83.7% of those mutations in the PMS2 gene would not have met NCCN criteria, Ms. Gay said.

Having a cancer type not known to be related to a genetic syndrome was a reason for 58.6% of individuals failing to meet NCCN guidelines, while 60.5% did not meet the guidelines because of an insufficient number of relatives known to have a history of cancer, and 63.3% did not because they had no personal history of cancer. Among individuals with a pathogenic mutation who met NCCN criteria, 34% were not aware of their condition.

“This suggests that the NCCN guidelines are underutilized in clinical practice, potentially due to the busy schedule of clinicians or because the complexity of using these criteria,” said Ms. Gay.

The numbers were even more striking among minorities: “There is additional data analysis and research needed in this area, but based on our preliminary findings, we saw that nearly 50% of the individuals who are [part of an underrepresented minority group] did not meet criteria, compared with 32% of the white cohort,” said Ms. Gay.

Asked what new NCCN guidelines should be, Ms. Gay replied: “I think maybe limiting the number of relatives that you have to have with a certain type of cancer, especially as we see families get smaller and smaller, especially in the United States – that family data isn’t necessarily available or as useful. And then also, I think, incorporating in the size of a family into the calculation, so more of maybe a point-based system like we see with other genetic conditions rather than a ‘yes you meet or no, you don’t.’ More of a range to say ‘you fall on the low-risk, medium-risk, or high-risk stage,’” said Ms. Gay.

During the Q&A period, session cochair Andrew Godwin, PhD, who is a professor of molecular oncology and pathology at University of Kansas Medical Center, Kansas City, said he wondered if whole-exome sequencing was capable of picking up cancer risk mutations that standard targeted tests don’t look for.

Dr. Samadder, who was in the audience, answered the question, saying that targeted tests are actually better at picking up some types of mutations like intronic mutations, single-nucleotide polymorphisms, and deletions.

“There are some limitations to whole-exome sequencing. Our estimate here of 1.2% [of participants carrying HBOC or LS mutations] is probably an underestimate. There are additional variants that exome sequencing probably doesn’t pick up easily or as well. That’s why we qualify that exome sequencing is a screening test, not a diagnostic,” he continued.

Ms. Gay and Dr. Samadder have no relevant financial disclosures. Dr. Godwin has financial relationships with Clara Biotech, VITRAC Therapeutics, and Sinochips Diagnostics.

A genetic sequencing effort identified more patients to be carriers of risk genes for hereditary breast and ovarian cancer or Lynch syndrome than would have been discovered by following existing genetic testing guidelines, according to new research.

The authors of the clinical trial suggest that these guidelines may need to be revised.

Individuals with hereditary breast and ovarian cancer (HBOC) have an 80% lifetime risk of breast cancer and are at greater risk of ovarian cancer, pancreatic cancer, prostate cancer, and melanoma. Those with Lynch syndrome (LS) have an 80% lifetime risk of colorectal cancer, a 60% lifetime risk of endometrial cancer, and heightened risk of upper gastrointestinal, urinary tract, skin, and other tumors, said study coauthor N. Jewel Samadder, MD in a statement.

The National Cancer Control Network has guidelines for determining family risk for colorectal cancer and breast, ovarian, and pancreatic cancer to identify individuals who should be screened for LS and HBOC, but these rely on personal and family health histories.

“These criteria were created at a time when genetic testing was cost prohibitive and thus aimed to identify those at the greatest chance of being a mutation carrier in the absence of population-wide whole-exome sequencing. However, [LS and HBOC] are poorly identified in current practice, and many patients are not aware of their cancer risk,” said Dr. Samadder, professor of medicine and coleader of the precision oncology program at the Mayo Clinic Comprehensive Cancer Center, Phoenix, in the statement.

Whole-exome sequencing covers only protein-coding regions of the genome, which is less than 2% of the total genome but includes more than 85% of known disease-related genetic variants, according to Emily Gay, who presented the trial results (Abstract 5768) on April 18 at the annual meeting of the American Association for Cancer Research.

“In recent years, the cost of whole-exome sequencing has been rapidly decreasing, allowing us to complete this test on saliva samples from thousands, if not tens of thousands of patients covering large populations and large health systems,” said Ms. Gay, a genetic counseling graduate student at the University of Arizona, during her presentation.

She described results from the TAPESTRY clinical trial, with 44,306 participants from Mayo Clinic centers in Arizona, Florida, and Minnesota, who were identified as definitely or likely to be harboring pathogenic mutations and consented to whole-exome sequencing from saliva samples. They used electronic health records to determine whether patients would satisfy the testing criteria from NCCN guidelines.

The researchers identified 1.24% of participants to be carriers of HBOC or LS. Of the HBOC carriers, 62.8% were female, and of the LS carriers, 62.6% were female. The percentages of HBOC and LS carriers who were White were 88.6 and 94.5, respectively. The median age of both groups was 57 years. Of HBOC carriers, 47.3% had personal histories of cancers; for LS carries, the percentage was 44.2.

Of HBOC carriers, 49.1% had been previously unaware of their genetic condition, while an even higher percentage of patients with LS – 59.3% – fell into that category. Thirty-two percent of those with HBOC and 56.2% of those with LS would not have qualified for screening using the relevant NCCN guidelines.

“Most strikingly,” 63.8% of individuals with mutations in the MSH6 gene and 83.7% of those mutations in the PMS2 gene would not have met NCCN criteria, Ms. Gay said.

Having a cancer type not known to be related to a genetic syndrome was a reason for 58.6% of individuals failing to meet NCCN guidelines, while 60.5% did not meet the guidelines because of an insufficient number of relatives known to have a history of cancer, and 63.3% did not because they had no personal history of cancer. Among individuals with a pathogenic mutation who met NCCN criteria, 34% were not aware of their condition.

“This suggests that the NCCN guidelines are underutilized in clinical practice, potentially due to the busy schedule of clinicians or because the complexity of using these criteria,” said Ms. Gay.

The numbers were even more striking among minorities: “There is additional data analysis and research needed in this area, but based on our preliminary findings, we saw that nearly 50% of the individuals who are [part of an underrepresented minority group] did not meet criteria, compared with 32% of the white cohort,” said Ms. Gay.

Asked what new NCCN guidelines should be, Ms. Gay replied: “I think maybe limiting the number of relatives that you have to have with a certain type of cancer, especially as we see families get smaller and smaller, especially in the United States – that family data isn’t necessarily available or as useful. And then also, I think, incorporating in the size of a family into the calculation, so more of maybe a point-based system like we see with other genetic conditions rather than a ‘yes you meet or no, you don’t.’ More of a range to say ‘you fall on the low-risk, medium-risk, or high-risk stage,’” said Ms. Gay.

During the Q&A period, session cochair Andrew Godwin, PhD, who is a professor of molecular oncology and pathology at University of Kansas Medical Center, Kansas City, said he wondered if whole-exome sequencing was capable of picking up cancer risk mutations that standard targeted tests don’t look for.

Dr. Samadder, who was in the audience, answered the question, saying that targeted tests are actually better at picking up some types of mutations like intronic mutations, single-nucleotide polymorphisms, and deletions.

“There are some limitations to whole-exome sequencing. Our estimate here of 1.2% [of participants carrying HBOC or LS mutations] is probably an underestimate. There are additional variants that exome sequencing probably doesn’t pick up easily or as well. That’s why we qualify that exome sequencing is a screening test, not a diagnostic,” he continued.

Ms. Gay and Dr. Samadder have no relevant financial disclosures. Dr. Godwin has financial relationships with Clara Biotech, VITRAC Therapeutics, and Sinochips Diagnostics.

A genetic sequencing effort identified more patients to be carriers of risk genes for hereditary breast and ovarian cancer or Lynch syndrome than would have been discovered by following existing genetic testing guidelines, according to new research.

The authors of the clinical trial suggest that these guidelines may need to be revised.

Individuals with hereditary breast and ovarian cancer (HBOC) have an 80% lifetime risk of breast cancer and are at greater risk of ovarian cancer, pancreatic cancer, prostate cancer, and melanoma. Those with Lynch syndrome (LS) have an 80% lifetime risk of colorectal cancer, a 60% lifetime risk of endometrial cancer, and heightened risk of upper gastrointestinal, urinary tract, skin, and other tumors, said study coauthor N. Jewel Samadder, MD in a statement.

The National Cancer Control Network has guidelines for determining family risk for colorectal cancer and breast, ovarian, and pancreatic cancer to identify individuals who should be screened for LS and HBOC, but these rely on personal and family health histories.

“These criteria were created at a time when genetic testing was cost prohibitive and thus aimed to identify those at the greatest chance of being a mutation carrier in the absence of population-wide whole-exome sequencing. However, [LS and HBOC] are poorly identified in current practice, and many patients are not aware of their cancer risk,” said Dr. Samadder, professor of medicine and coleader of the precision oncology program at the Mayo Clinic Comprehensive Cancer Center, Phoenix, in the statement.

Whole-exome sequencing covers only protein-coding regions of the genome, which is less than 2% of the total genome but includes more than 85% of known disease-related genetic variants, according to Emily Gay, who presented the trial results (Abstract 5768) on April 18 at the annual meeting of the American Association for Cancer Research.

“In recent years, the cost of whole-exome sequencing has been rapidly decreasing, allowing us to complete this test on saliva samples from thousands, if not tens of thousands of patients covering large populations and large health systems,” said Ms. Gay, a genetic counseling graduate student at the University of Arizona, during her presentation.

She described results from the TAPESTRY clinical trial, with 44,306 participants from Mayo Clinic centers in Arizona, Florida, and Minnesota, who were identified as definitely or likely to be harboring pathogenic mutations and consented to whole-exome sequencing from saliva samples. They used electronic health records to determine whether patients would satisfy the testing criteria from NCCN guidelines.

The researchers identified 1.24% of participants to be carriers of HBOC or LS. Of the HBOC carriers, 62.8% were female, and of the LS carriers, 62.6% were female. The percentages of HBOC and LS carriers who were White were 88.6 and 94.5, respectively. The median age of both groups was 57 years. Of HBOC carriers, 47.3% had personal histories of cancers; for LS carries, the percentage was 44.2.

Of HBOC carriers, 49.1% had been previously unaware of their genetic condition, while an even higher percentage of patients with LS – 59.3% – fell into that category. Thirty-two percent of those with HBOC and 56.2% of those with LS would not have qualified for screening using the relevant NCCN guidelines.

“Most strikingly,” 63.8% of individuals with mutations in the MSH6 gene and 83.7% of those mutations in the PMS2 gene would not have met NCCN criteria, Ms. Gay said.

Having a cancer type not known to be related to a genetic syndrome was a reason for 58.6% of individuals failing to meet NCCN guidelines, while 60.5% did not meet the guidelines because of an insufficient number of relatives known to have a history of cancer, and 63.3% did not because they had no personal history of cancer. Among individuals with a pathogenic mutation who met NCCN criteria, 34% were not aware of their condition.

“This suggests that the NCCN guidelines are underutilized in clinical practice, potentially due to the busy schedule of clinicians or because the complexity of using these criteria,” said Ms. Gay.

The numbers were even more striking among minorities: “There is additional data analysis and research needed in this area, but based on our preliminary findings, we saw that nearly 50% of the individuals who are [part of an underrepresented minority group] did not meet criteria, compared with 32% of the white cohort,” said Ms. Gay.

Asked what new NCCN guidelines should be, Ms. Gay replied: “I think maybe limiting the number of relatives that you have to have with a certain type of cancer, especially as we see families get smaller and smaller, especially in the United States – that family data isn’t necessarily available or as useful. And then also, I think, incorporating in the size of a family into the calculation, so more of maybe a point-based system like we see with other genetic conditions rather than a ‘yes you meet or no, you don’t.’ More of a range to say ‘you fall on the low-risk, medium-risk, or high-risk stage,’” said Ms. Gay.

During the Q&A period, session cochair Andrew Godwin, PhD, who is a professor of molecular oncology and pathology at University of Kansas Medical Center, Kansas City, said he wondered if whole-exome sequencing was capable of picking up cancer risk mutations that standard targeted tests don’t look for.

Dr. Samadder, who was in the audience, answered the question, saying that targeted tests are actually better at picking up some types of mutations like intronic mutations, single-nucleotide polymorphisms, and deletions.

“There are some limitations to whole-exome sequencing. Our estimate here of 1.2% [of participants carrying HBOC or LS mutations] is probably an underestimate. There are additional variants that exome sequencing probably doesn’t pick up easily or as well. That’s why we qualify that exome sequencing is a screening test, not a diagnostic,” he continued.

Ms. Gay and Dr. Samadder have no relevant financial disclosures. Dr. Godwin has financial relationships with Clara Biotech, VITRAC Therapeutics, and Sinochips Diagnostics.

Cancer screening remains challenging. There are screens available for a handful of solid tumors, but uptake is low caused in part by health care access barriers as well as the potential for unnecessary follow-up procedures, according to Phillip Febbo, MD.

These issues could threaten efforts like that of President Joe Biden’s Cancer Moonshot initiative, which aims to reduce cancer mortality by 50%. Advances in circulating tumor (ct) DNA analysis could help address these problems, but a lack of diversity among study participants needs to be addressed to ensure it has broad utility, continued Dr. Febbo, during his presentation at the annual meeting of the American Association for Cancer Research.

The problem is particularly acute among African American, Hispanic, and other underserved populations who often face health care barriers that can exacerbate the issue, said Dr. Febbo, who is chief medical officer for Illumina. The lack of access is compounded by the fact that there are only currently screens for lung, breast, colorectal, cervical, and prostate cancer, leaving a vast unmet need.

“We still do not have screening tests for 70% of the deaths that are due to cancer,” he said.

ctDNA released from dying cancer cells has the potential to reveal a wide range of cancer types and reduce barriers to access, because it is based on a blood test. It can be analyzed for various factors, including mutations, chromosomal rearrangements, methylation patterns, and other characteristics that hint at the presence of cancer. However, it can’t be successful without sufficient inclusion in research studies, Dr. Febbo explained.

“We have to ensure we have the right representation [of] populations when we develop these tests, when we go through the clinical trials, and as we bring these into communities,” he said.

During his presentation, Dr. Febbo shared a slide showing that about 78% of participants in published gene-association studies were White.

ctDNA showed promise in at least on recent study. Dr. Febbo discussed the ECLIPSE trial, which used the Guardant Health SHIELD assay for colorectal cancer (CRC). About 13% of its approximately 20,000 participants were Black or African American, 15% were Hispanic, and 7% were Asian Americans. It also included both urban and rural individuals. In results announced in December 2022, the researchers found a sensitivity of 83%, which was lower than the 92.3% found in standard CRC screening, but above the 74% threshold set by the Food and Drug Administration. The specificity was 90%.

One approach that could dramatically change the landscape of cancer screening is a multicancer early detection (MCED) test, according to Dr. Febbo. The CancerSeek MCED test, developed by Johns Hopkins Kimmel Cancer Center researchers, uses a series of genetic and protein biomarkers to detect all cancers, with the exception of leukemia, skin cancer, and central nervous system tumors. Among 10,006 women aged between 65 and 75 years with no history of cancer, it had a sensitivity of 27.1% and a specificity of 98.9%, with a positive predictive value of 19.4%. The study’s population was 95% non-Hispanic White.

He also discussed the Pathfinder study, sponsored by the Illumina subsidiary Grail, which included 6,662 individuals age 50 and over from seven sites in the United States, and grouped them into normal and increased risk; 92% were non-Hispanic White. It used the Galleri MCED test, which performed with a sensitivity of 29%, specificity of 99.1%, and a positive predictive value of 38.0%. False positives produced to limited burden, with 93% undergoing imaging, 28% nonsurgical invasive procedures, and 2% undergoing fruitless invasive surgical procedures.

Dr. Febbo touted the potential for such tests to greatly reduce cancer mortality, but only if there is adequate uptake of screening procedures, particularly in underserved groups. He put up a slide of a model showing that MCED has the potential to reduce cancer mortality by 20%, but only if the screen is widely accepted among all groups. “I’ve had my team model this. If we accept the current use of screening tests, and we don’t address disparities, and we don’t ensure everybody feels included and participates actively – not only in the research, but also in the testing and adoption, you would cut that potential benefit in half. That would be hundreds of thousands of lives lost because we didn’t address disparities.”
 

Successful recruiting of African Americans for research

Following Dr. Febbo’s talk, Karriem Watson, MS, spoke about some potential solutions to the issue, including his own experiences and success stories in recruiting African Americans to play active roles in research. He is chief engagement officer for the National Institute of Health’s All of Us Research Program, which aims to gather health data on at least 1 million residents of the United States. Mr. Watson has spent time reaching out to people living in communities in the Chicago area to encourage participation in breast cancer screening. An event at his church inspired his own sister to get a mammogram, and she was diagnosed with early-stage breast cancer.

“I’m a living witness that early engagement can lead to early detection,” said Mr. Watson during his talk.

He reported that the All of Us research program has succeeded in creating diversity within its data collection, as 46.7% of participants identify as racial and ethnic minorities.

Mr. Watson took issue with the common perception that underrepresented communities may be hard to reach.

“I want to challenge us to think outside the box and really ask ourselves: Are populations hard to reach, or are there opportunities for us to do better and more intentional engagement?” He went on to describe a program to recruit African American men as citizen scientists. He and his colleagues developed a network that included barbers, faith leaders, and fraternity and civic organization members to help recruit participants for a prostate cancer screening project. They exceeded their initial recruitment goal.

They went on to develop a network of barbers in the south and west sides of Chicago to recruit individuals to participate in studies of protein methylation and lung cancer screening, as well as a project that investigated associations between neighborhood of residence and lung cancer. The results of those efforts have also informed other projects, including a smoking cessation study. “We’ve not only included African American men in our research, but we’ve included them as part of our research team,” said Mr. Watson.

Dr. Febbo is also a stockholder of Illumina. Mr. Watson has no relevant financial disclosures.

From American Association for Cancer Research (AACR) Annual Meeting 2023: Improving cancer outcomes through equitable access to cfDNA tests. Presented Monday, April 17, 2023.

Cancer screening remains challenging. There are screens available for a handful of solid tumors, but uptake is low caused in part by health care access barriers as well as the potential for unnecessary follow-up procedures, according to Phillip Febbo, MD.

These issues could threaten efforts like that of President Joe Biden’s Cancer Moonshot initiative, which aims to reduce cancer mortality by 50%. Advances in circulating tumor (ct) DNA analysis could help address these problems, but a lack of diversity among study participants needs to be addressed to ensure it has broad utility, continued Dr. Febbo, during his presentation at the annual meeting of the American Association for Cancer Research.

The problem is particularly acute among African American, Hispanic, and other underserved populations who often face health care barriers that can exacerbate the issue, said Dr. Febbo, who is chief medical officer for Illumina. The lack of access is compounded by the fact that there are only currently screens for lung, breast, colorectal, cervical, and prostate cancer, leaving a vast unmet need.

“We still do not have screening tests for 70% of the deaths that are due to cancer,” he said.

ctDNA released from dying cancer cells has the potential to reveal a wide range of cancer types and reduce barriers to access, because it is based on a blood test. It can be analyzed for various factors, including mutations, chromosomal rearrangements, methylation patterns, and other characteristics that hint at the presence of cancer. However, it can’t be successful without sufficient inclusion in research studies, Dr. Febbo explained.

“We have to ensure we have the right representation [of] populations when we develop these tests, when we go through the clinical trials, and as we bring these into communities,” he said.

During his presentation, Dr. Febbo shared a slide showing that about 78% of participants in published gene-association studies were White.

ctDNA showed promise in at least on recent study. Dr. Febbo discussed the ECLIPSE trial, which used the Guardant Health SHIELD assay for colorectal cancer (CRC). About 13% of its approximately 20,000 participants were Black or African American, 15% were Hispanic, and 7% were Asian Americans. It also included both urban and rural individuals. In results announced in December 2022, the researchers found a sensitivity of 83%, which was lower than the 92.3% found in standard CRC screening, but above the 74% threshold set by the Food and Drug Administration. The specificity was 90%.

One approach that could dramatically change the landscape of cancer screening is a multicancer early detection (MCED) test, according to Dr. Febbo. The CancerSeek MCED test, developed by Johns Hopkins Kimmel Cancer Center researchers, uses a series of genetic and protein biomarkers to detect all cancers, with the exception of leukemia, skin cancer, and central nervous system tumors. Among 10,006 women aged between 65 and 75 years with no history of cancer, it had a sensitivity of 27.1% and a specificity of 98.9%, with a positive predictive value of 19.4%. The study’s population was 95% non-Hispanic White.

He also discussed the Pathfinder study, sponsored by the Illumina subsidiary Grail, which included 6,662 individuals age 50 and over from seven sites in the United States, and grouped them into normal and increased risk; 92% were non-Hispanic White. It used the Galleri MCED test, which performed with a sensitivity of 29%, specificity of 99.1%, and a positive predictive value of 38.0%. False positives produced to limited burden, with 93% undergoing imaging, 28% nonsurgical invasive procedures, and 2% undergoing fruitless invasive surgical procedures.

Dr. Febbo touted the potential for such tests to greatly reduce cancer mortality, but only if there is adequate uptake of screening procedures, particularly in underserved groups. He put up a slide of a model showing that MCED has the potential to reduce cancer mortality by 20%, but only if the screen is widely accepted among all groups. “I’ve had my team model this. If we accept the current use of screening tests, and we don’t address disparities, and we don’t ensure everybody feels included and participates actively – not only in the research, but also in the testing and adoption, you would cut that potential benefit in half. That would be hundreds of thousands of lives lost because we didn’t address disparities.”
 

Successful recruiting of African Americans for research

Following Dr. Febbo’s talk, Karriem Watson, MS, spoke about some potential solutions to the issue, including his own experiences and success stories in recruiting African Americans to play active roles in research. He is chief engagement officer for the National Institute of Health’s All of Us Research Program, which aims to gather health data on at least 1 million residents of the United States. Mr. Watson has spent time reaching out to people living in communities in the Chicago area to encourage participation in breast cancer screening. An event at his church inspired his own sister to get a mammogram, and she was diagnosed with early-stage breast cancer.

“I’m a living witness that early engagement can lead to early detection,” said Mr. Watson during his talk.

He reported that the All of Us research program has succeeded in creating diversity within its data collection, as 46.7% of participants identify as racial and ethnic minorities.

Mr. Watson took issue with the common perception that underrepresented communities may be hard to reach.

“I want to challenge us to think outside the box and really ask ourselves: Are populations hard to reach, or are there opportunities for us to do better and more intentional engagement?” He went on to describe a program to recruit African American men as citizen scientists. He and his colleagues developed a network that included barbers, faith leaders, and fraternity and civic organization members to help recruit participants for a prostate cancer screening project. They exceeded their initial recruitment goal.

They went on to develop a network of barbers in the south and west sides of Chicago to recruit individuals to participate in studies of protein methylation and lung cancer screening, as well as a project that investigated associations between neighborhood of residence and lung cancer. The results of those efforts have also informed other projects, including a smoking cessation study. “We’ve not only included African American men in our research, but we’ve included them as part of our research team,” said Mr. Watson.

Dr. Febbo is also a stockholder of Illumina. Mr. Watson has no relevant financial disclosures.

From American Association for Cancer Research (AACR) Annual Meeting 2023: Improving cancer outcomes through equitable access to cfDNA tests. Presented Monday, April 17, 2023.

Cancer screening remains challenging. There are screens available for a handful of solid tumors, but uptake is low caused in part by health care access barriers as well as the potential for unnecessary follow-up procedures, according to Phillip Febbo, MD.

These issues could threaten efforts like that of President Joe Biden’s Cancer Moonshot initiative, which aims to reduce cancer mortality by 50%. Advances in circulating tumor (ct) DNA analysis could help address these problems, but a lack of diversity among study participants needs to be addressed to ensure it has broad utility, continued Dr. Febbo, during his presentation at the annual meeting of the American Association for Cancer Research.

The problem is particularly acute among African American, Hispanic, and other underserved populations who often face health care barriers that can exacerbate the issue, said Dr. Febbo, who is chief medical officer for Illumina. The lack of access is compounded by the fact that there are only currently screens for lung, breast, colorectal, cervical, and prostate cancer, leaving a vast unmet need.

“We still do not have screening tests for 70% of the deaths that are due to cancer,” he said.

ctDNA released from dying cancer cells has the potential to reveal a wide range of cancer types and reduce barriers to access, because it is based on a blood test. It can be analyzed for various factors, including mutations, chromosomal rearrangements, methylation patterns, and other characteristics that hint at the presence of cancer. However, it can’t be successful without sufficient inclusion in research studies, Dr. Febbo explained.

“We have to ensure we have the right representation [of] populations when we develop these tests, when we go through the clinical trials, and as we bring these into communities,” he said.

During his presentation, Dr. Febbo shared a slide showing that about 78% of participants in published gene-association studies were White.

ctDNA showed promise in at least on recent study. Dr. Febbo discussed the ECLIPSE trial, which used the Guardant Health SHIELD assay for colorectal cancer (CRC). About 13% of its approximately 20,000 participants were Black or African American, 15% were Hispanic, and 7% were Asian Americans. It also included both urban and rural individuals. In results announced in December 2022, the researchers found a sensitivity of 83%, which was lower than the 92.3% found in standard CRC screening, but above the 74% threshold set by the Food and Drug Administration. The specificity was 90%.

One approach that could dramatically change the landscape of cancer screening is a multicancer early detection (MCED) test, according to Dr. Febbo. The CancerSeek MCED test, developed by Johns Hopkins Kimmel Cancer Center researchers, uses a series of genetic and protein biomarkers to detect all cancers, with the exception of leukemia, skin cancer, and central nervous system tumors. Among 10,006 women aged between 65 and 75 years with no history of cancer, it had a sensitivity of 27.1% and a specificity of 98.9%, with a positive predictive value of 19.4%. The study’s population was 95% non-Hispanic White.

He also discussed the Pathfinder study, sponsored by the Illumina subsidiary Grail, which included 6,662 individuals age 50 and over from seven sites in the United States, and grouped them into normal and increased risk; 92% were non-Hispanic White. It used the Galleri MCED test, which performed with a sensitivity of 29%, specificity of 99.1%, and a positive predictive value of 38.0%. False positives produced to limited burden, with 93% undergoing imaging, 28% nonsurgical invasive procedures, and 2% undergoing fruitless invasive surgical procedures.

Dr. Febbo touted the potential for such tests to greatly reduce cancer mortality, but only if there is adequate uptake of screening procedures, particularly in underserved groups. He put up a slide of a model showing that MCED has the potential to reduce cancer mortality by 20%, but only if the screen is widely accepted among all groups. “I’ve had my team model this. If we accept the current use of screening tests, and we don’t address disparities, and we don’t ensure everybody feels included and participates actively – not only in the research, but also in the testing and adoption, you would cut that potential benefit in half. That would be hundreds of thousands of lives lost because we didn’t address disparities.”
 

Successful recruiting of African Americans for research

Following Dr. Febbo’s talk, Karriem Watson, MS, spoke about some potential solutions to the issue, including his own experiences and success stories in recruiting African Americans to play active roles in research. He is chief engagement officer for the National Institute of Health’s All of Us Research Program, which aims to gather health data on at least 1 million residents of the United States. Mr. Watson has spent time reaching out to people living in communities in the Chicago area to encourage participation in breast cancer screening. An event at his church inspired his own sister to get a mammogram, and she was diagnosed with early-stage breast cancer.

“I’m a living witness that early engagement can lead to early detection,” said Mr. Watson during his talk.

He reported that the All of Us research program has succeeded in creating diversity within its data collection, as 46.7% of participants identify as racial and ethnic minorities.

Mr. Watson took issue with the common perception that underrepresented communities may be hard to reach.

“I want to challenge us to think outside the box and really ask ourselves: Are populations hard to reach, or are there opportunities for us to do better and more intentional engagement?” He went on to describe a program to recruit African American men as citizen scientists. He and his colleagues developed a network that included barbers, faith leaders, and fraternity and civic organization members to help recruit participants for a prostate cancer screening project. They exceeded their initial recruitment goal.

They went on to develop a network of barbers in the south and west sides of Chicago to recruit individuals to participate in studies of protein methylation and lung cancer screening, as well as a project that investigated associations between neighborhood of residence and lung cancer. The results of those efforts have also informed other projects, including a smoking cessation study. “We’ve not only included African American men in our research, but we’ve included them as part of our research team,” said Mr. Watson.

Dr. Febbo is also a stockholder of Illumina. Mr. Watson has no relevant financial disclosures.

From American Association for Cancer Research (AACR) Annual Meeting 2023: Improving cancer outcomes through equitable access to cfDNA tests. Presented Monday, April 17, 2023.

Key clinical point: Achievement of pathologic complete response (pCR) or residual tumor cellularity (RTC) <40% is associated with improved survival outcomes in patients with breast cancer (BC) who have received neoadjuvant chemotherapy (NAC).

Major finding: Early clinical stage (cT1-2), human epidermal growth factor receptor 2-positive BC subtype, and absence of vascular invasion predicted the achievement of pCR after NAC (all P  =  .001). Patients who achieved pCR vs pathologic partial response (pPR) had significantly longer overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS; all P < .001). However, among patients with pPR, RTC <40% vs ≥40% was associated with significantly longer DFS (P  =  .033) and DDFS (P  =  .015).

Study details: Findings are from a retrospective analysis including 495 patients with BC who underwent NAC, of which 29.9% of patients achieved pCR.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Gentile D et al. Pathologic response and residual tumor cellularity after neo-adjuvant chemotherapy predict prognosis in breast cancer patients. Breast. 2023;69:323-329 (Mar 27). Doi: 10.1016/j.breast.2023.03.016

Key clinical point: Achievement of pathologic complete response (pCR) or residual tumor cellularity (RTC) <40% is associated with improved survival outcomes in patients with breast cancer (BC) who have received neoadjuvant chemotherapy (NAC).

Major finding: Early clinical stage (cT1-2), human epidermal growth factor receptor 2-positive BC subtype, and absence of vascular invasion predicted the achievement of pCR after NAC (all P  =  .001). Patients who achieved pCR vs pathologic partial response (pPR) had significantly longer overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS; all P < .001). However, among patients with pPR, RTC <40% vs ≥40% was associated with significantly longer DFS (P  =  .033) and DDFS (P  =  .015).

Study details: Findings are from a retrospective analysis including 495 patients with BC who underwent NAC, of which 29.9% of patients achieved pCR.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Gentile D et al. Pathologic response and residual tumor cellularity after neo-adjuvant chemotherapy predict prognosis in breast cancer patients. Breast. 2023;69:323-329 (Mar 27). Doi: 10.1016/j.breast.2023.03.016

Key clinical point: Achievement of pathologic complete response (pCR) or residual tumor cellularity (RTC) <40% is associated with improved survival outcomes in patients with breast cancer (BC) who have received neoadjuvant chemotherapy (NAC).

Major finding: Early clinical stage (cT1-2), human epidermal growth factor receptor 2-positive BC subtype, and absence of vascular invasion predicted the achievement of pCR after NAC (all P  =  .001). Patients who achieved pCR vs pathologic partial response (pPR) had significantly longer overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS; all P < .001). However, among patients with pPR, RTC <40% vs ≥40% was associated with significantly longer DFS (P  =  .033) and DDFS (P  =  .015).

Study details: Findings are from a retrospective analysis including 495 patients with BC who underwent NAC, of which 29.9% of patients achieved pCR.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Gentile D et al. Pathologic response and residual tumor cellularity after neo-adjuvant chemotherapy predict prognosis in breast cancer patients. Breast. 2023;69:323-329 (Mar 27). Doi: 10.1016/j.breast.2023.03.016

Key clinical point: Preterm birth was positively associated with the risk for incident premenopausal breast cancer (BC) in women aged <55 years who experienced preeclampsia or gestational hypertension.

Major finding: Overall, a history of preterm birth was not associated with the risk for premenopausal BC (hazard ratio [HR] 1.02; 95% CI 0.92-1.14). However, it was positively associated with the risk for premenopausal BC in women who had preeclampsia or gestational hypertension (HR 1.52; 95% CI 1.06-2.18). Preeclampsia on the other hand was inversely associated with premenopausal BC risk (HR 0.86; 95% CI 0.75-0.99).

Study details: Findings are from an analysis of six cohort studies including 184,866 premenopausal women aged <55 years, of which 3096 women were diagnosed with premenopausal BC.

Disclosures: This study was supported by the US National Institutes of Health and other sources. The authors declared no conflicts of interest.

Source: Nichols HB et al. Hypertensive conditions of pregnancy, preterm birth, and premenopausal breast cancer risk: A premenopausal breast cancer collaborative group analysis. Breast Cancer Res Treat. 2023 (Apr 5). Doi: 10.1007/s10549-023-06903-5

Key clinical point: Preterm birth was positively associated with the risk for incident premenopausal breast cancer (BC) in women aged <55 years who experienced preeclampsia or gestational hypertension.

Major finding: Overall, a history of preterm birth was not associated with the risk for premenopausal BC (hazard ratio [HR] 1.02; 95% CI 0.92-1.14). However, it was positively associated with the risk for premenopausal BC in women who had preeclampsia or gestational hypertension (HR 1.52; 95% CI 1.06-2.18). Preeclampsia on the other hand was inversely associated with premenopausal BC risk (HR 0.86; 95% CI 0.75-0.99).

Study details: Findings are from an analysis of six cohort studies including 184,866 premenopausal women aged <55 years, of which 3096 women were diagnosed with premenopausal BC.

Disclosures: This study was supported by the US National Institutes of Health and other sources. The authors declared no conflicts of interest.

Source: Nichols HB et al. Hypertensive conditions of pregnancy, preterm birth, and premenopausal breast cancer risk: A premenopausal breast cancer collaborative group analysis. Breast Cancer Res Treat. 2023 (Apr 5). Doi: 10.1007/s10549-023-06903-5

Key clinical point: Preterm birth was positively associated with the risk for incident premenopausal breast cancer (BC) in women aged <55 years who experienced preeclampsia or gestational hypertension.

Major finding: Overall, a history of preterm birth was not associated with the risk for premenopausal BC (hazard ratio [HR] 1.02; 95% CI 0.92-1.14). However, it was positively associated with the risk for premenopausal BC in women who had preeclampsia or gestational hypertension (HR 1.52; 95% CI 1.06-2.18). Preeclampsia on the other hand was inversely associated with premenopausal BC risk (HR 0.86; 95% CI 0.75-0.99).

Study details: Findings are from an analysis of six cohort studies including 184,866 premenopausal women aged <55 years, of which 3096 women were diagnosed with premenopausal BC.

Disclosures: This study was supported by the US National Institutes of Health and other sources. The authors declared no conflicts of interest.

Source: Nichols HB et al. Hypertensive conditions of pregnancy, preterm birth, and premenopausal breast cancer risk: A premenopausal breast cancer collaborative group analysis. Breast Cancer Res Treat. 2023 (Apr 5). Doi: 10.1007/s10549-023-06903-5

Key clinical point: Sonography features, such as spiculated morphology and antiparallel orientation, were significantly associated with worsened survival outcomes in patients with primary breast cancer (BC; tumor size <20 mm).

Major finding: The presence of spiculated morphology and antiparallel orientation on ultrasound was a significant risk factor for poor breast cancer-specific survival (hazard ratio [HR] 7.45; P < .001) and disease-free survival (HR 6.42; P < .001), with age ≥55 years (P < .05) and positive lymph node metastases (P < .001) also being associated with worse prognosis.

Study details: Findings are from a retrospective study including 790 women with small primary BC (tumor size <20 mm).

Disclosures: This study was supported by the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Shao S et al. Ultrasound features for prediction of long-term outcomes of women with primary breast cancer <20 mm. Front Oncol. 2023;13:1103397 (Mar 16). Doi: 10.3389/fonc.2023.1103397

Key clinical point: Sonography features, such as spiculated morphology and antiparallel orientation, were significantly associated with worsened survival outcomes in patients with primary breast cancer (BC; tumor size <20 mm).

Major finding: The presence of spiculated morphology and antiparallel orientation on ultrasound was a significant risk factor for poor breast cancer-specific survival (hazard ratio [HR] 7.45; P < .001) and disease-free survival (HR 6.42; P < .001), with age ≥55 years (P < .05) and positive lymph node metastases (P < .001) also being associated with worse prognosis.

Study details: Findings are from a retrospective study including 790 women with small primary BC (tumor size <20 mm).

Disclosures: This study was supported by the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Shao S et al. Ultrasound features for prediction of long-term outcomes of women with primary breast cancer <20 mm. Front Oncol. 2023;13:1103397 (Mar 16). Doi: 10.3389/fonc.2023.1103397

Key clinical point: Sonography features, such as spiculated morphology and antiparallel orientation, were significantly associated with worsened survival outcomes in patients with primary breast cancer (BC; tumor size <20 mm).

Major finding: The presence of spiculated morphology and antiparallel orientation on ultrasound was a significant risk factor for poor breast cancer-specific survival (hazard ratio [HR] 7.45; P < .001) and disease-free survival (HR 6.42; P < .001), with age ≥55 years (P < .05) and positive lymph node metastases (P < .001) also being associated with worse prognosis.

Study details: Findings are from a retrospective study including 790 women with small primary BC (tumor size <20 mm).

Disclosures: This study was supported by the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Shao S et al. Ultrasound features for prediction of long-term outcomes of women with primary breast cancer <20 mm. Front Oncol. 2023;13:1103397 (Mar 16). Doi: 10.3389/fonc.2023.1103397

Key clinical point: Breast-conserving surgery without axillary lymph node dissection as well as breast and axillary radiotherapy (BCSNR) was safe and resulted in survival rates comparable to mastectomy plus axillary lymph node dissection (MALND) in elderly patients with axillary lymph node-negative breast cancer (BC).

Major finding: At a median follow-up of 5 years, BCSNR vs MALND was not associated with significantly worsened distant recurrence-free survival (98.1% vs 93.2%; P  =  .990) and BC-specific survival (96.3% vs 99.3%; P  =  .076) rates but was associated with a significantly higher local recurrence rate (10.3% vs 2.2%; P  =  .001).

Study details: Findings are from a retrospective study including 541 patients aged ≥70 years with axillary lymph node-negative BC, of which 181 and 360 patients underwent MALND with negative axillary cleaning and BCSNR, respectively.

Disclosures: This study was supported by the CAMS Innovation Fund for Medical Sciences, China, and other sources. The authors declared no conflicts of interest.

Source: Zhong Y et al. Breast-conserving surgery without axillary surgery and radiation versus mastectomy plus axillary dissection in elderly breast cancer patients: A retrospective study. Front Oncol. 2023;13:1126104 (Mar 20). Doi: 10.3389/fonc.2023.1126104

Key clinical point: Breast-conserving surgery without axillary lymph node dissection as well as breast and axillary radiotherapy (BCSNR) was safe and resulted in survival rates comparable to mastectomy plus axillary lymph node dissection (MALND) in elderly patients with axillary lymph node-negative breast cancer (BC).

Major finding: At a median follow-up of 5 years, BCSNR vs MALND was not associated with significantly worsened distant recurrence-free survival (98.1% vs 93.2%; P  =  .990) and BC-specific survival (96.3% vs 99.3%; P  =  .076) rates but was associated with a significantly higher local recurrence rate (10.3% vs 2.2%; P  =  .001).

Study details: Findings are from a retrospective study including 541 patients aged ≥70 years with axillary lymph node-negative BC, of which 181 and 360 patients underwent MALND with negative axillary cleaning and BCSNR, respectively.

Disclosures: This study was supported by the CAMS Innovation Fund for Medical Sciences, China, and other sources. The authors declared no conflicts of interest.

Source: Zhong Y et al. Breast-conserving surgery without axillary surgery and radiation versus mastectomy plus axillary dissection in elderly breast cancer patients: A retrospective study. Front Oncol. 2023;13:1126104 (Mar 20). Doi: 10.3389/fonc.2023.1126104

Key clinical point: Breast-conserving surgery without axillary lymph node dissection as well as breast and axillary radiotherapy (BCSNR) was safe and resulted in survival rates comparable to mastectomy plus axillary lymph node dissection (MALND) in elderly patients with axillary lymph node-negative breast cancer (BC).

Major finding: At a median follow-up of 5 years, BCSNR vs MALND was not associated with significantly worsened distant recurrence-free survival (98.1% vs 93.2%; P  =  .990) and BC-specific survival (96.3% vs 99.3%; P  =  .076) rates but was associated with a significantly higher local recurrence rate (10.3% vs 2.2%; P  =  .001).

Study details: Findings are from a retrospective study including 541 patients aged ≥70 years with axillary lymph node-negative BC, of which 181 and 360 patients underwent MALND with negative axillary cleaning and BCSNR, respectively.

Disclosures: This study was supported by the CAMS Innovation Fund for Medical Sciences, China, and other sources. The authors declared no conflicts of interest.

Source: Zhong Y et al. Breast-conserving surgery without axillary surgery and radiation versus mastectomy plus axillary dissection in elderly breast cancer patients: A retrospective study. Front Oncol. 2023;13:1126104 (Mar 20). Doi: 10.3389/fonc.2023.1126104

Key clinical point: Serum thymidine kinase 1 activity (sTKa) proved to be an excellent biomarker of progression risk in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (BC) receiving first-line ribociclib+letrozole.

Major finding: Disease progression risk was significantly higher in patients with high vs low sTKa levels at baseline (hazard ratio 2.21; P  =  .0002). Patients with high sTKa levels on day 1 of cycle 2 after initial decrease on day 15 of cycle 1 (C1D15; hazard ratio 2.89; P  =  .0006) or on C1D15 (hazard ratio 5.65; P < .0001) had worse prognosis than those with low sTKa levels at all time points.

Study details: This phase 3 BioItaLEE study included 287 postmenopausal women with HR+/HER2– advanced BC who received ribociclib+letrozole as first-line therapy.

Disclosures: This study was supported by Novartis Farma SpA, Italy. Some authors declared participating on advisory boards and receiving grants, fees, honoraria, or travel support from several sources, including Novartis.

Source: Malorni L et al. Serum thymidine kinase activity in patients with HR-positive/HER2-negative advanced breast cancer treated with ribociclib plus letrozole: Results from the prospective BioItaLEE trial. Eur J Cancer. 2023;186:1-11 (Mar 7). Doi: 10.1016/j.ejca.2023.03.001

Key clinical point: Serum thymidine kinase 1 activity (sTKa) proved to be an excellent biomarker of progression risk in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (BC) receiving first-line ribociclib+letrozole.

Major finding: Disease progression risk was significantly higher in patients with high vs low sTKa levels at baseline (hazard ratio 2.21; P  =  .0002). Patients with high sTKa levels on day 1 of cycle 2 after initial decrease on day 15 of cycle 1 (C1D15; hazard ratio 2.89; P  =  .0006) or on C1D15 (hazard ratio 5.65; P < .0001) had worse prognosis than those with low sTKa levels at all time points.

Study details: This phase 3 BioItaLEE study included 287 postmenopausal women with HR+/HER2– advanced BC who received ribociclib+letrozole as first-line therapy.

Disclosures: This study was supported by Novartis Farma SpA, Italy. Some authors declared participating on advisory boards and receiving grants, fees, honoraria, or travel support from several sources, including Novartis.

Source: Malorni L et al. Serum thymidine kinase activity in patients with HR-positive/HER2-negative advanced breast cancer treated with ribociclib plus letrozole: Results from the prospective BioItaLEE trial. Eur J Cancer. 2023;186:1-11 (Mar 7). Doi: 10.1016/j.ejca.2023.03.001

Key clinical point: Serum thymidine kinase 1 activity (sTKa) proved to be an excellent biomarker of progression risk in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (BC) receiving first-line ribociclib+letrozole.

Major finding: Disease progression risk was significantly higher in patients with high vs low sTKa levels at baseline (hazard ratio 2.21; P  =  .0002). Patients with high sTKa levels on day 1 of cycle 2 after initial decrease on day 15 of cycle 1 (C1D15; hazard ratio 2.89; P  =  .0006) or on C1D15 (hazard ratio 5.65; P < .0001) had worse prognosis than those with low sTKa levels at all time points.

Study details: This phase 3 BioItaLEE study included 287 postmenopausal women with HR+/HER2– advanced BC who received ribociclib+letrozole as first-line therapy.

Disclosures: This study was supported by Novartis Farma SpA, Italy. Some authors declared participating on advisory boards and receiving grants, fees, honoraria, or travel support from several sources, including Novartis.

Source: Malorni L et al. Serum thymidine kinase activity in patients with HR-positive/HER2-negative advanced breast cancer treated with ribociclib plus letrozole: Results from the prospective BioItaLEE trial. Eur J Cancer. 2023;186:1-11 (Mar 7). Doi: 10.1016/j.ejca.2023.03.001

Key clinical point: In a pre-cyclin-dependent kinase 4 and 6 inhibitors era, patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancer (BC) who had BRCA1/2 germline mutation (gBRCAm) vs wild type (gBRCAwt) had worse survival outcomes, especially those who received first-line endocrine therapy (ET).

Major finding: Compared with gBRCAwt carriers, gBRCAm carriers had shorter overall survival (OS; adjusted hazard ratio [aHR] 1.26; P  =  .024) and progression-free survival (PFS; aHR 1.21; P  =  .017), with both OS (aHR 1.54; P  =  .037) and PFS (aHR 1.58; P  =  .003) being further attenuated in patients receiving first-line ET.

Study details: Findings are from a study including 13,776 patients with metastatic BC from the ESME (Épidémio-Stratégie Médico-Economique) metastatic BC database, of which 676 and 170 patients were gBRCAwt and gBRCAm carriers, respectively.

Disclosures: The ESME metastatic BC database received financial support from various sources. Some authors declared receiving grants, personal fees, or non-financial support, or having other ties with several sources.

Source: Frenel JS et al. Efficacy of front-line treatment for hormone receptor-positive HER2-negative metastatic breast cancer with germline BRCA1/2 mutation. Br J Cancer. 2023 (Apr 3). Doi: 10.1038/s41416-023-02248-4

Key clinical point: In a pre-cyclin-dependent kinase 4 and 6 inhibitors era, patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancer (BC) who had BRCA1/2 germline mutation (gBRCAm) vs wild type (gBRCAwt) had worse survival outcomes, especially those who received first-line endocrine therapy (ET).

Major finding: Compared with gBRCAwt carriers, gBRCAm carriers had shorter overall survival (OS; adjusted hazard ratio [aHR] 1.26; P  =  .024) and progression-free survival (PFS; aHR 1.21; P  =  .017), with both OS (aHR 1.54; P  =  .037) and PFS (aHR 1.58; P  =  .003) being further attenuated in patients receiving first-line ET.

Study details: Findings are from a study including 13,776 patients with metastatic BC from the ESME (Épidémio-Stratégie Médico-Economique) metastatic BC database, of which 676 and 170 patients were gBRCAwt and gBRCAm carriers, respectively.

Disclosures: The ESME metastatic BC database received financial support from various sources. Some authors declared receiving grants, personal fees, or non-financial support, or having other ties with several sources.

Source: Frenel JS et al. Efficacy of front-line treatment for hormone receptor-positive HER2-negative metastatic breast cancer with germline BRCA1/2 mutation. Br J Cancer. 2023 (Apr 3). Doi: 10.1038/s41416-023-02248-4

Key clinical point: In a pre-cyclin-dependent kinase 4 and 6 inhibitors era, patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancer (BC) who had BRCA1/2 germline mutation (gBRCAm) vs wild type (gBRCAwt) had worse survival outcomes, especially those who received first-line endocrine therapy (ET).

Major finding: Compared with gBRCAwt carriers, gBRCAm carriers had shorter overall survival (OS; adjusted hazard ratio [aHR] 1.26; P  =  .024) and progression-free survival (PFS; aHR 1.21; P  =  .017), with both OS (aHR 1.54; P  =  .037) and PFS (aHR 1.58; P  =  .003) being further attenuated in patients receiving first-line ET.

Study details: Findings are from a study including 13,776 patients with metastatic BC from the ESME (Épidémio-Stratégie Médico-Economique) metastatic BC database, of which 676 and 170 patients were gBRCAwt and gBRCAm carriers, respectively.

Disclosures: The ESME metastatic BC database received financial support from various sources. Some authors declared receiving grants, personal fees, or non-financial support, or having other ties with several sources.

Source: Frenel JS et al. Efficacy of front-line treatment for hormone receptor-positive HER2-negative metastatic breast cancer with germline BRCA1/2 mutation. Br J Cancer. 2023 (Apr 3). Doi: 10.1038/s41416-023-02248-4

Key clinical point: In women with noninvasive neoplasia of the breast, treatment with low-dose tamoxifen for 3 years continued to prevent breast cancer (BC) recurrence, with an optimal safety profile, for at least 7 years after treatment cessation.

Major finding: After a median follow-up of 9.7 years, fewer cases of both invasive and in-situ BC (hazard ratio [HR] 0.58; log-rank P  =  .03) and contralateral BC (HR 0.36; P  =  .025) were reported in the tamoxifen vs placebo group. There was no increase in serious adverse events during tamoxifen therapy.

Study details: Findings are from a 10-year follow-up analysis of the phase 3 TAM-01 trial including 500 women with intraepithelial neoplasia of the breast who were randomly assigned to receive low-dose tamoxifen or placebo.

Disclosures: This study was supported by the Italian Ministry of Health and other sources. The authors declared serving as employees, consultants, or advisors, or receiving honoraria and travel and accommodation expenses from several sources.

Source: Lazzeroni M et al. Randomized placebo controlled trial of low-dose tamoxifen to prevent recurrence in breast noninvasive neoplasia: A 10-year follow-up of TAM-01 study. J Clin Oncol. 2023 (Mar 14). Doi: 10.1200/JCO.22.02900

Key clinical point: In women with noninvasive neoplasia of the breast, treatment with low-dose tamoxifen for 3 years continued to prevent breast cancer (BC) recurrence, with an optimal safety profile, for at least 7 years after treatment cessation.

Major finding: After a median follow-up of 9.7 years, fewer cases of both invasive and in-situ BC (hazard ratio [HR] 0.58; log-rank P  =  .03) and contralateral BC (HR 0.36; P  =  .025) were reported in the tamoxifen vs placebo group. There was no increase in serious adverse events during tamoxifen therapy.

Study details: Findings are from a 10-year follow-up analysis of the phase 3 TAM-01 trial including 500 women with intraepithelial neoplasia of the breast who were randomly assigned to receive low-dose tamoxifen or placebo.

Disclosures: This study was supported by the Italian Ministry of Health and other sources. The authors declared serving as employees, consultants, or advisors, or receiving honoraria and travel and accommodation expenses from several sources.

Source: Lazzeroni M et al. Randomized placebo controlled trial of low-dose tamoxifen to prevent recurrence in breast noninvasive neoplasia: A 10-year follow-up of TAM-01 study. J Clin Oncol. 2023 (Mar 14). Doi: 10.1200/JCO.22.02900

Key clinical point: In women with noninvasive neoplasia of the breast, treatment with low-dose tamoxifen for 3 years continued to prevent breast cancer (BC) recurrence, with an optimal safety profile, for at least 7 years after treatment cessation.

Major finding: After a median follow-up of 9.7 years, fewer cases of both invasive and in-situ BC (hazard ratio [HR] 0.58; log-rank P  =  .03) and contralateral BC (HR 0.36; P  =  .025) were reported in the tamoxifen vs placebo group. There was no increase in serious adverse events during tamoxifen therapy.

Study details: Findings are from a 10-year follow-up analysis of the phase 3 TAM-01 trial including 500 women with intraepithelial neoplasia of the breast who were randomly assigned to receive low-dose tamoxifen or placebo.

Disclosures: This study was supported by the Italian Ministry of Health and other sources. The authors declared serving as employees, consultants, or advisors, or receiving honoraria and travel and accommodation expenses from several sources.

Source: Lazzeroni M et al. Randomized placebo controlled trial of low-dose tamoxifen to prevent recurrence in breast noninvasive neoplasia: A 10-year follow-up of TAM-01 study. J Clin Oncol. 2023 (Mar 14). Doi: 10.1200/JCO.22.02900