Risk Of Primary Cancer Research Articles

Recall patterns and risk of primary liver cancer for subcentimeter ultrasound liver observations: a multicenter study

Patients with cirrhosis and subcentimeter lesions on liver ultrasound are recommended to undergo short-interval follow-up ultrasound because of the presumed low risk of primary liver cancer (PLC). The aim of this study is to characterize recall patterns and risk of PLC in patients with subcentimeter liver lesions on ultrasound. We conducted a multicenter retrospective cohort study among patients with cirrhosis or chronic hepatitis B infection who had subcentimeter ultrasound lesions between January 2017 and December 2019. We excluded patients with a history of PLC or concomitant lesions ≥1cm in diameter. We used Kaplan Meier and multivariable Cox regression analyses to characterize time-to-PLC and factors associated with PLC, respectively. Of 746 eligible patients, most (66.0%) had a single observation, and the median diameter was 0.7cm (interquartile range: 0.5-0.8cm). Recall strategies varied, with only 27.8% of patients undergoing guideline-concordant ultrasound within 3-6 months. Over a median follow-up of 26 months, 42 patients developed PLC (39 HCC and 3 cholangiocarcinoma), yielding an incidence of 25.7 cases (95% CI, 6.2-47.0) per 1000 person-years, with 3.9% and 6.7% developing PLC at 2 and 3 years, respectively. Factors associated with time-to-PLC were baseline alpha-fetoprotein >10ng/mL (HR: 4.01, 95% CI, 1.85-8.71), platelet count ≤150 (HR: 4.90, 95% CI, 1.95-12.28), and Child-Pugh B cirrhosis (vs. Child-Pugh A: HR: 2.54, 95% CI, 1.27-5.08). Recall patterns for patients with subcentimeter liver lesions on ultrasound varied widely. The low risk of PLC in these patients supports short-interval ultrasound in 3-6 months, although diagnostic CT/MRI may be warranted for high-risk subgroups such as those with elevated alpha-fetoprotein levels.

Abstract P3-05-12: A matched cohort study of the prognosis of early breast cancer in patients with Li-Fraumeni syndrome

Abstract Background: Patients with germline TP53 pathogenic variants (Li-Fraumeni syndrome - LFS) have an increased risk of breast cancer, which is the most common type of cancer in premenopausal women with LFS. These women are also at risk of other second malignancies, including radiotherapy-induced malignancies. On the other hand, little is known about the prognosis of breast cancer in patients with LFS or if the disease behavior differs from non-hereditary BC. The objective of this study was to characterize the phenotype and prognosis of early BC in patients with LFS compared to a matched cohort of patients without germline pathogenic variants (PV) related to BC. Methods: This retrospective study evaluated patients with early BC treated in an academic cancer center from Dec 1999 to Mar 2022. The LFS cohort included consecutive patients with BC who harbored a PV or likely PV of TP53. The matched control cohort (2:1) included patients with BC with no germline PV in a panel test. Primary endpoint was disease-free survival (DFS). Since LFS is associated with an increased risk of new primary malignancies, only locoregional and distant BC recurrence were considered as events in the DFS analysis. Secondary endpoints included response to systemic therapy, sites of recurrence, and breast cancer-related deaths. Results: Forty-six patients with LFS were evaluated; the control cohort included 91 matched patients. In the LFS cohort, 14 different PV or likely PV were identified, with TP53 p.R337H being the most common (n=32). Median age was 40 years in both groups. In the LFS cohort, 35% of the pts had HER2-positive BC compared to 21% in the control cohort. Primary tumors greater than 5 cm were observed in 15% of pts in the LFS cohort and 25% of pts in the control cohort. Positive lymph nodes were observed in 11% and 14%, respectively. Among 15 pts with LFS who received neoadjuvant chemotherapy, all (100%) had a response, with 5 (33%) complete responses. Thirty-five patients in the control group received neoadjuvant chemotherapy: 83% responded, with 11 (31%) presenting a complete response. With a median follow-up of 43 months, 5-year DFS rates were 82.6% (95% CI 65.1 – 91.9%) in the LFS cohort and 91.5% (95% CI 79.1 – 96.6%) in the control cohort (P=0.427). Rates and sites of recurrence, new primary BC, and deaths are detailed in the table. Conclusions: In addition to a higher risk of new primary breast cancer, LFS patients with early breast cancer had numerically higher rates of locoregional and distant recurrence in comparison with a matched cohort. Nevertheless, further studies are required to understand if these differences are due to tumor behavior particularities or to differences in therapeutic management. Recurrence and death events Citation Format: Vanessa Petry, Renata Colombo Bonadio, Daniela Jafet, Roberta Campos, Luiz Senna, Allyne Cagnacci, Laura Testa, Maria Candida Villares Fragoso, Maria del Pilar Estevez Diz. A matched cohort study of the prognosis of early breast cancer in patients with Li-Fraumeni syndrome [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-12.

Abstract P3-03-17: The Impact of Cardiovascular Disease Risk on Cancer Progression among Female Breast Cancer Survivors: A Longitudinal Study within The Boss Cohort

Abstract Background Among breast cancer (BC) survivors, cardiovascular disease (CVD) is one of the most common comorbidities contributing to mortality. Data on to what extent CVD risk impacts disease progression and second cancers in younger women is limited. We conducted a prospective cohort study to examine whether CVD risk is associated with disease recurrence or new primary cancer among female BC survivors enrolled in a cohort of women with a family history of BC. Methods The study included 301 females with a first primary diagnosis of BC in the Breast and Ovarian Surveillance Service (BOSS) Cohort, after excluding those who had a history of recurrence or second primary cancer prior to enrollment (N=125), a diagnosis of ductal carcinoma in situ (DCIS) (N=66), and with missing CVD risk factors (N=3). A risk score based on 7 CVD risk factors (age 65 or older, diabetes, hypertension, high cholesterol, body mass index (BMI), smoking status, and physical activity) was assessed at baseline and updated 4 and 8 years after enrollment. Each risk factor was given a score (0, 1, or 2) and was summed and categorized into low (score=0 or 1), intermediate (score=2 or 3), and high (score >3) risk. The primary outcome was either BC progression or all second primary cancers. Analyses limited to BC progression and second BC only were also conducted. Outcomes were ascertained through active follow-up and confirmed by pathology records. Kaplan-Meier graphs and two different Cox regression models were used to compare risk groups: model 1 adjusted for participants’ age, race, BMI, time from diagnosis, education, tumor stage, and estrogen receptor (ER) status; model 2 included further adjustment of cancer treatments (chemotherapy, hormone therapy, radiation), statin use, baby aspirin use, and specifically cardiotoxic treatments. For subgroup analyses, a more parsimonious model was used including age, race, BMI, education, cancer treatments, and cardiotoxic treatment. Results Participants’ mean age of BC diagnosis was 47.4 years and the median follow-up time was 11.5 years. The incidence rate of recurrence or any second cancer was 21 cases per 1000 person-years. At baseline, there were 168, 130, and 84 survivors in the low, intermediate, and high CVD risk groups respectively, and their use of statins increased from 12.7%, 34.5% to 52.7%. In the multivariable model, BC survivors with an intermediate CVD risk score had a 2.23 times greater risk of recurrence or second primary cancer as compared to those with a low CVD risk score (95% CI=1.20- 4.17). After further adjusting for cancer and CVD treatment in model 2, the HR was attenuated but still significant to 2.01 (95% CI = 1.20- 4.17. Interestingly, the association was attenuated and non-significant in the high-risk group (model 2: HR=1.37, 95% CI = 0.54- 3.45). The positive association between intermediate CVD risk score and recurrence or second cancer was also observed among subgroups of BC survivors including those who were postmenopausal (HR = 2.23, 95% CI = 1.01-4.93), with ER-positive BC (HR=2.07, 95% CI=1.08-3.99), regional disease (HR = 2.74, 95% CI = 1.06-7.04), diagnosed 5 years or greater (HR = 4.85, 95% CI = 1.14-20.66). There was a significant interaction between intermediated CVD risk and diagnosis time of 5 years (P interaction = 0.033). Restricting the outcome to disease progression and second BC alone led to similar results. The HR comparing the intermediate risk group and low risk group was 2.65 (95% CI = 1.27-5.55) in model 1 and decreased to 2.28 (95% CI = 1.06-4.89) in model 2. Conclusion There was a significant association between CVD risk and subsequent cancer progression in female breast cancer survivors, particularly among long-term BC survivors. The non-significant results among the women with high CVD risk scores may reflect the fact that a greater proportion of these women compared to women in the intermediate group reported taking cardiac treatments that can favorably impact cancer progression. Citation Format: Xinyi Feng, Zhengyi Deng, Michelle McCollough, Betty May, Erica Selznick, Avonne Connor, Deborah K. Armstrong, Kala Visvanathan. The Impact of Cardiovascular Disease Risk on Cancer Progression among Female Breast Cancer Survivors: A Longitudinal Study within The Boss Cohort [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-17.

Abstract OT2-13-01: Willingness to Participate in a Trial Comparing Standard Genetic Counseling versus Genetic Counseling with Personalized Cancer Risks Estimates in Patients with Li-Fraumeni Syndrome

Abstract Background: Individuals with Li-Fraumeni Syndrome (LFS) have increased risk of developing breast cancer, sarcomas, brain tumors, leukemia, and other cancers throughout their lifetime. LFS is primarily caused by autosomal dominant germline mutations in the TP53 tumor suppressor gene. Due to the large number of cancers caused by LFS, and their variable age of presentation, each LFS family often presents very differently. Currently, standard genetic counseling for patients with LFS often involves general lifetime risk predictions for developing several primary cancers. At present, there are no standard tools available to help genetics providers obtain a personalized risk assessment for a patient with LFS based on their unique personal and family history data. To address this, the LFSPRO risk model was developed to estimate the likelihood of a proband having LFS, to provide cancer-specific risks of a first primary cancer, and to estimate risk of time to second primary cancer diagnosis by utilizing detailed personal and family history information. Specific Aims: This study aims to understand patients’ willingness to participate in a randomized trial comparing standard genetic counseling practice to personalized genetic counseling via LFSPRO risk estimates. Trial Design: Eligible patients or parents/guardians are invited via email to complete a survey assessing interest in a hypothetical clinical trial scenario where patients are randomized to receive one of two types of post-disclosure genetic counseling approaches: standard genetic counseling for TP53 results, involving generic risk predictions for developing cancers, or personalized risk information provided from LFSPRO. Following the hypothetical scenario, participants are asked about their perceived benefits and barriers to this research scenario and interest in receiving personalized risk results. Demographic information is also collected. Eligibility Criteria: Individuals who receive genetic counseling through MD Anderson Cancer Center genetics clinics specifically for TP53 genetic testing and who consent to undergo TP53 genetic testing or individuals who genetic testing already indicates a TP53 germline mutation are offered this survey. Patients must be 13 years or older to complete the survey, otherwise a parent/guardian may complete the survey on their behalf. Patients must have English fluency. Statistical methods: Descriptive statistics will be used to analyze the data and summarize the opinion of the participants. Accrual: Enrollment is set to open in July 2022. Currently, 157 patients have been identified to be invited to participate in the study. Funding: This research is supported by the Cancer Research and Prevention Institute of Texas. Contact: Jacynda Woodman-Ross, MS, CGC, The University of Texas MD Anderson Cancer Center, jawoodman@mdanderson.org Citation Format: Jacynda Woodman-Ross, Sierra O. Green, Jessica Corredor, Elissa Dodd-Eaton, Nathaniel Hernandez, Susan K. Peterson, Wenyi Wang, Banu K. Arun. Willingness to Participate in a Trial Comparing Standard Genetic Counseling versus Genetic Counseling with Personalized Cancer Risks Estimates in Patients with Li-Fraumeni Syndrome [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-13-01.

Perceptions of Breast Cancer Risks Among Women Receiving Mammograph Screening

Breast density is an independent risk factor for breast cancer. Despite the proliferation of mandated written notifications about breast density following mammography, there is little understanding of how women perceive the relative breast cancer risk associated with breast density. To assess women's perception of breast density compared with other breast cancer risks and explore their understanding of risk reduction. This mixed-methods qualitative study used telephone surveys and semistructured interviews to investigate perceptions about breast cancer risk among a nationally representative, population-based sample of women. Eligible study participants were aged 40 to 76 years, reported having recently undergone mammography, had no history of prior breast cancer, and had heard of breast density. Survey participants who had been informed of their personal breast density were invited for a qualitative interview. Survey administration spanned July 1, 2019, to April 30, 2020, with 2306 women completing the survey. Qualitative interviews were conducted from February 1 to May 30, 2020. Respondents compared the breast cancer risk associated with breast density with 5 other risk factors. Participants qualitatively described what they thought contributed to breast cancer risk and ways to reduce risk. Of the 2306 women who completed the survey, 1858 (166 [9%] Asian, 503 [27%] Black, 268 [14%] Hispanic, 792 [43%] White, and 128 [7%] other race or ethnicity; 358 [19%] aged 40-49 years, 906 [49%] aged 50-64 years, and 594 [32%] aged ≥65 years) completed the revised risk perception questions and were included in the analysis. Half of respondents thought breast density to be a greater risk than not having children (957 [52%]), having more than 1 alcoholic drink per day (975 [53%]), or having a prior breast biopsy (867 [48%]). Most respondents felt breast density was a lesser risk than having a first-degree relative with breast cancer (1706 [93%]) or being overweight or obese (1188 [65%]). Of the 61 women who were interviewed, 6 (10%) described breast density as contributing to breast cancer risk, and 43 (70%) emphasized family history as a breast cancer risk factor. Of the interviewed women, 17 (28%) stated they did not know whether it was possible to reduce their breast cancer risk. In this qualitative study of women of breast cancer screening age, family history was perceived as the primary breast cancer risk factor. Most interviewees did not identify breast density as a risk factor and did not feel confident about actions to mitigate breast cancer risk. Comprehensive education about breast cancer risks and prevention strategies is needed.

Sociodemographic, clinical and survival profile of adult metastatic patients.

To characterize the sociodemographic, clinical and survival profile of adult metastatic patients. Retrospective cross-sectional study, with secondary data from an oncology care unit, analyzed using logistic regression, Chi-Square test and Fisher's exact test, Kaplan-Meier and Log-Rank tests. From the 678 patients, male gender, mean age 59.54 years old and low education level prevailed. The mean time between diagnosis and initiation of treatment was 89.50 days (± 58.87). Increased risk of primary cancer in the digestive tract (OR 1.42). Prevalence of adenocarcinoma (OR 1.53) and metastasis to bone (OR 2.59), lymph nodes (OR 1.75), liver and peritoneum (OR 1.42). The mean overall survival was 4.16 months and a median of 3.0 months. The main primary site was the digestive system, and the identification of metastases was predominantly unifocal liver in both genders. Overall patient survival was reduced by cancer progression.

Effectiveness of Secondary Risk–Reducing Strategies in Patients With Unilateral Breast Cancer With Pathogenic Variants of BRCA1 and BRCA2 Subjected to Breast-Conserving Surgery: Evidence-Based Simulation Study

Approximately 62% of patients with breast cancer with a pathogenic variant (BRCA1 or BRCA2) undergo primary breast-conserving therapy. The study aims to develop a personalized risk management decision support tool for carriers of a pathogenic variant (BRCA1 or BRCA2) who underwent breast-conserving therapy for unilateral early-stage breast cancer. We developed a Bayesian network model of a hypothetical cohort of carriers of BRCA1 or BRCA2 diagnosed with stage I/II unilateral breast cancer and treated with breast-conserving treatment who underwent subsequent second primary cancer risk-reducing strategies. Using event dependencies structured according to expert knowledge and conditional probabilities obtained from published evidence, we predicted the 40-year overall survival rate of different risk-reducing strategies for 144 cohorts of women defined by the type of pathogenic variants (BRCA1 or BRCA2), age at primary breast cancer diagnosis, breast cancer subtype, stage of primary breast cancer, and presence or absence of adjuvant chemotherapy. Absence of adjuvant chemotherapy was the most powerful factor that was linked to a dramatic decline in survival. There was a negligible decline in the mortality in patients with triple-negative breast cancer, who received no chemotherapy and underwent any secondary risk-reducing strategy, compared with surveillance. The potential survival benefit from any risk-reducing strategy was more modest in patients with triple-negative breast cancer who received chemotherapy compared with patients with luminal breast cancer. However, most patients with triple-negative breast cancer in stage I benefited from bilateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy or just risk-reducing salpingo-oophorectomy. Most patients with luminal stage I/II unilateral breast cancer benefited from bilateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy. The impact of risk-reducing salpingo-oophorectomy in patients with luminal breast cancer in stage I/II increased with age. Most older patients with the BRCA1 and BRCA2 pathogenic variants in exons 12-24/25 with luminal breast cancer may gain a similar survival benefit from other risk-reducing strategies or surveillance. Our study showed that it is mandatory to consider the complex interplay between the types of BRCA1 and BRCA2 pathogenic variants, age at primary breast cancer diagnosis, breast cancer subtype and stage, and received systemic treatment. As no prospective study results are available at the moment, our simulation model, which will integrate a decision support system in the near future, could facilitate the conversation between the health care provider and patient and help to weigh all the options for risk-reducing strategies leading to a more balanced decision.

Aspirin and Primary Cancer Risk Reduction in Ischemic Cardiac or Cerebrovascular Disease Survivors: A Nationwide Population-Based Propensity-Matched Cohort Study.

Ischemic cardiac or cerebrovascular disease (ICCD) survivors represent a subpopulation with a high cancer risk. Antiplatelet medications, such as aspirin, remain a fundamental therapy for the secondary prevention of ischemic attack in these patients. We conducted a population-based cohort study to investigate the association of long-term low-dose aspirin use with the risk of primary cancer in ICCD survivors. Patients aged ≥20 years with newly diagnosed ICCD (n = 98,519) between January 2000 and December 2013 were identified from the Taiwan National Health Insurance Research Database. The aspirin user and nonuser groups (each n = 24,030) were propensity-matched (1:1) for age, sex, comorbidities, prior medications, ICCD diagnosis year, and year of index dates. The incidence rate of primary cancer was significantly lower in the user group (6.49/1000 person-years) than in the nonuser group (14.04/1000 person-years). Multivariate Cox regression analysis indicated that aspirin use was an independent factor associated with a reduced risk of primary cancer (aHR (95% confidence interval) = 0.42 (0.38−0.45)) after adjustment. Kaplan−Meier curve analysis revealed that the cumulative incidence rate of primary cancer was significantly lower (p < 0.0001) in the user group than in the nonuser group over the 14-year follow-up period. Subgroup analyses demonstrated that this anticancer effect increased with duration of treatment and with similar estimates in women and men. In addition, aspirin use was associated with a reduced risk for seven out of the ten most common cancers in Taiwan. These findings suggest the anticancer effect of aspirin in ICCD survivors and provide information for assessing the benefit-to-risk profile of aspirin as an antiplatelet medication in these patients.

Associations between serum glucose, insulin, insulin resistance and the risk of incident primary liver cancer or chronic liver disease mortality: a nested case-control study.

To evaluate the associations between pre-diagnostic levels of serum insulin, glucose and insulin resistance (HOMA-IR) and future risk of incident primary liver cancer (PLC) or chronic liver disease (CLD)-related mortality. We used a nested case-control design to evaluate subjects over 22 years of follow-up. Glucose, insulin, and three markers of hepatitis B virus (HBV) and hepatitis C virus were measured in fasting baseline serum from 119 incident PLCs, 157 CLD-death cases and 512 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression to estimate the associations between insulin, glucose, HOMA-IR and the risk of PLC or CLD death. Compared with the lowest quartile of insulin, multivariable adjusted models showed that subjects in the highest quartile had elevated odds of developing PLC (ORQ4/Q1 = 2.42, 95% CI = 1.26-4.75, Ptrend = 0.007), particularly in HBV-positive subjects (Pinteraction = 0.040), and of CLD death (ORQ4/Q1 = 1.80, 95% CI = 1.02-3.21, Ptrend = 0.018). For glucose, in the HBV-positive group, subjects in the fourth quartile had an increased risk of PLC (ORQ4/Q1 = 2.18, 95% CI = 1.07-4.60, Ptrend = 0.009), and of CLD mortality (ORQ4/Q1 = 1.75, 95% CI = 0.95-3.28, Ptrend = 0.019). Subjects with the highest HOMA-IR values had a threefold risk of developing PLC (ORQ4/Q1 = 2.94, 95% CI = 1.54-5.87, Ptrend = 0.001), and a twofold risk of CLD death (ORQ4/Q1 = 2.20, 95% CI = 1.25-3.94, Ptrend = 0.005). We found that serum insulin and HOMA-IR could potentially be risk factors for PLC or CLD death.

Risk of primary haematologic cancers following incident non-metastatic breast cancer: A Danish population-based cohort study

BackgroundBreast cancer survivors may have increased risk of subsequent haematologic cancer. We compared their risk of haematologic cancers with the general population during 38 years of follow-up. MethodsUsing population-based Danish medical registries, we assembled a nationwide cohort of women diagnosed with incident non-metastatic breast cancer during 1980–2017, with follow-up through 2018. We compared breast cancer survivors with the general population by computing standardised incidence ratios (SIR) and 95% confidence intervals (CI). ResultsAmong 101,117 breast cancer survivors, we observed 815 incident haematologic cancers (median follow-up: 7.9 years). We observed excess risk of acute myeloid leukaemia (AML) (SIR: 1.65, 95%CI: 1.33–2.01), particularly in women who received chemotherapy (SIR: 3.33, 95%CI: 2.24–4.75) and premenopausal women (SIR: 3.23, 95%CI: 2.41–4.25). The risk of acute lymphoid leukaemia (ALL) was increased (SIR: 2.25, 95%CI: 1.29–3.66), whereas the risk of chronic lymphoid leukaemia (CLL) was decreased (SIR: 0.66, 95%CI: 0.53–0.82). An additional analysis showed elevated risk of CLL 0–6 months after breast cancer diagnosis (SIR: 3.00 95%CI: 1.75–4.80). ConclusionCompared to the general population, breast cancer survivors had elevated risk of AML, particularly when treated with chemotherapy. The risk of ALL was elevated, whereas the risk of CLL was lower. The higher risk of CLL in the first six months after diagnosis likely reflects surveillance bias—due to intensified diagnostic efforts at breast cancer diagnosis and treatment—prompting earlier detection. This has likely reduced the long-term risk of CLL in breast cancer survivors.

The etiology of adnexal masses in women with a history of non-gynaecological malignancy: recurrence, second, primary or none?

The occurrence of adnexal masses in patients with a history of non-gynaecological malignancy (NGM) raises concerns for malignancy, either primary or metastasis. Subsequent treatment and prognosis depends on the etiology. Our aim was to investigate the characteristics and results of the patients with suspicious adnexal masses, who had a history of NGM. The records of 61 patients with a history of NGM were analyzed, who were operated for an adnexal mass. Complex adnexal masses were included in the analysis while simple cysts were excluded. The most common NGM origins were gastrointestinal (gastric and colorectal) tract and breast. Of all adnexal masses, four were benign (6.5%), 22 were primary ovarian malignancy (36.1%) and 35 were metastasis (57.4%). Two of the 22 primary cases were borderline ovarian tumor. Among the characteristics of primary and metastatic groups, laterality in pathology results and serum CA125 levels were statistically different (p<0.05). Among the patients with history of gastrointestinal cancers, the percentage of ovarian metastasis was 81%. Primary ovarian malignancy was most frequently (64%) observed among the patients with history of breast cancers. For patients with a history of gastrointestinal cancer, recurrence of the cancer in the form of ovarian metastasis was more likely, rather than a second primary cancer. The risk of primary ovarian cancer (POC) was remarkable in those with history of a breast cancer. A multidisciplinary strategy, including a gynaecological oncologist, plays an important role in managing these cases, regardless of whether or not it is a POC.

Immediate Breast Reconstruction Using the Autologous Dermal Flap

IntroductionDespite the development of breast-conserving surgery in breast cancer treatment, there still remain indications for total mastectomy. Since mastectomy has a significant negative impact on the patients’ quality of life, breast reconstruction is increasingly popular. However, for patients with large ptotic breasts who do not choose tissue-based reconstruction techniques and prefer implant-based breast reconstruction, there is no single-stage breast reconstruction technique other than the classic technique using Acellular Dermal Matrix (ADM). MethodsThis study presents a novel technique for Nipple-Sparing Mastectomy (NSM) and Immediate Breast reconstruction (IBR) in 11 operations (in seven patients) whose treatment decision-making was based on NCCN guidelines. In this technique, the implant/tissue expander is covered by the pectoral muscle in the upper part and an autologous dermal flap in the lower part, replacing an ADM. The dermal flap is created from the de-epithelialized lower mastectomy flap in these large ptotic breasts. Maintaining the nipple-areola complex (NAC) is possible by re-implanting a free nipple split-thickness graft from the NAC of the ipsilateral breast prepared at the beginning of the operation. ResultsAll seven patients had large ptotic breasts ranging from C cup to double D in size and grade 2 and higher breast ptosis. The mean BMI of the patients was 28 (range: 26-33). No major complications occurred postoperatively. There were three minor complications, all managed conservatively. Surgical indications were risk reduction surgery in three patients with BRCA mutations and therapeutic in the remaining patients (three multifocal invasive ductal carcinomas and one diffused ductal carcinoma in situ). None of the patients had a previous reduction mammoplasty as preparation for NSM, and all the patients underwent a single operation. No breast tissue remained under the NAC, which is ideal with the NSM technique. ConclusionsThe proposed technique is excellent for implant-based IBR in patients with large ptotic breasts. It eliminates the use of ADM mesh and reduces the cost and postoperative complication rate associated with ADM. Furthermore, using a free nipple graft technique can eliminate the need for a preparatory mastopexy. This technique can also theoretically reduce the risk of recurrence or new primary breast cancer as there are no remaining ducts beneath the nipple-areola complex.

Risk of subsequent primary oral cancer in a cohort of 69,460 5-year survivors of childhood and adolescent cancer in Europe: the PanCareSurFup study

BackgroundSurvivors of childhood cancer are at risk of subsequent primary malignant neoplasms (SPNs), but the risk for rarer types of SPNs, such as oral cancer, is uncertain. Previous studies included few oral SPNs, hence large-scale cohorts are required to identify groups at risks.MethodsThe PanCareSurFup cohort includes 69,460 5-year survivors of childhood cancer across Europe. Risks of oral SPNs were defined by standardised incidence ratios (SIRs), absolute excess risks and cumulative incidence.ResultsOne hundred and forty-five oral SPNs (64 salivary gland, 38 tongue, 20 pharynx, 2 lip, and 21 other) were ascertained among 143 survivors. Survivors were at 5-fold risk of an oral SPN (95% CI: 4.4–5.6). Survivors of leukaemia were at greatest risk (SIR = 19.2; 95% CI: 14.6–25.2) followed by bone sarcoma (SIR = 6.4, 95% CI: 3.7–11.0), Hodgkin lymphoma (SIR = 6.2, 95% CI: 3.9–9.9) and soft-tissue sarcoma (SIR = 5.0, 95% CI: 3.0–8.5). Survivors treated with radiotherapy were at 33-fold risk of salivary gland SPNs (95% CI: 25.3–44.5), particularly Hodgkin lymphoma (SIR = 66.2, 95% CI: 43.6–100.5) and leukaemia (SIR = 50.5, 95% CI: 36.1–70.7) survivors. Survivors treated with chemotherapy had a substantially increased risk of a tongue SPN (SIR = 15.9, 95% CI: 10.6–23.7).ConclusionsPrevious radiotherapy increases the risk of salivary gland SPNs considerably, while chemotherapy increases the risk of tongue SPNs substantially. Awareness of these risks among both health-care professionals and survivors could play a crucial role in detecting oral SPNs early.

Risk of subsequent primary oral cancer in a cohort of 69,460 5-year survivors of childhood and adolescent cancer in Europe: the PanCareSurFup study

Risk of subsequent primary oral cancer in a cohort of 69,460 5-year survivors of childhood and adolescent cancer in Europe: the PanCareSurFup study

36 (PB-036) Poster - Second primary cancer risks for female and male breast cancer survivors in England

Background: Second primary cancer (SPC) incidence is significantly increased following breast cancer (BC) diagnosis, but the magnitudes of these risks remain unclear. We estimated SPC risks following BC separately for males and females based on comprehensive data from linkage of National Cancer Registration and Analysis (NCRAS) and Hospital Episode Statistics (HES) electronic health records in England.

Radiation Therapy for Stage IIA/B Seminoma: Modeling Secondary Cancer Risk for Protons and VMAT vs. 3D Photons

<h3>Purpose/Objective(s)</h3> Radiation therapy to the para-aortic and iliac lymph nodes is an effective treatment for stage IIA and appropriately selected stage IIB seminoma patients. However, there are concerns for serious late complications, particularly an increased risk of secondary cancers due to the large areas of normal tissue irradiated. The purpose of this study was to quantify the expected differences in secondary cancer risk for stage II seminomas when evaluating proton pencil-beam scanning (PBS) and volumetric modulated arc therapy (VMAT) compared to conventional AP-PA photon (3D) treatment plans. <h3>Materials/Methods</h3> Five seminoma patients (four stage IIA receiving 30 Gy and one stage IIB receiving 36 Gy) ranging in age from 38 to 48 (mean 41.2) treated at our institution with PBS had two additional plans generated for comparison— one photon VMAT and one photon 3D. Dose differences to critical organs were examined and the risks of second primary cancers in those organs were calculated as the Excess Absolute Risk (EAR), reported in cancers per 10,000 person years, and Lifetime Attributable Risk (LAR), reported in percentage increase in risk, both projected to age 70. <h3>Results</h3> PBS reduced the mean organ dose compared to photons, on average by 60% but ranging from 30%-95% for different organs, except for the spinal cord which received the lowest mean dose with VMAT. PBS also reduced the EAR for all organs, with the greatest reduction for large and small bowel, liver, and stomach. Table 1 shows the average ratio of LAR between PBS, 3D, and VMAT for critical organs in five patients, and this ratio is greater than 1 for all organs for 3D compared to PBS. VMAT plans provide a mean dose reduction to some critical organs compared to 3D, particularly the spinal cord and pancreas, where VMAT also reduces the LAR compared to PBS. However, VMAT increases the low dose bath through other organs, leading to slightly increased LAR for the bladder, liver, and rectum compared to 3D. <h3>Conclusion</h3> The use of protons in stage IIA/B seminoma provides a favorable dose distribution with an expectation that this will transfer into decreased toxicity and reduced secondary cancer risk compared to conventional 3D photons. VMAT is another alternative to conventional 3D photons that provides a reduction in dose to some critical organs and comparable or reduced secondary cancer risk predictions for most organs.

Links between Breast and Thyroid Cancer: Hormones, Genetic Susceptibility and Medical Interventions.

Simple SummaryBreast and thyroid cancer are commonly diagnosed in women. Physicians have recognized and evaluated the phenomenon of two cancers occurring synchronously or asynchronously. The potential mechanisms are complex and various. Hormone, autoimmune attack and genetic predisposition are significant and shared factors influencing two cancers. Medical interventions for the first cancer and other life-related factors are reviewed and discussed, as well. This article aims to expound the relationship between breast and thyroid cancer, and suggests that physicians should monitor for the second cancer appropriately whenever one cancer occurs.Breast and thyroid glands are two common sites of female malignancies. Since the late 19th century, physicians have found that the cancers in either thyroid or mammary gland might increase the risk of second primary cancers in the other site. From then on, many observational clinical studies have confirmed the hypothesis and more than one theory has been developed to explain the phenomenon. Since the two glands both have secretory functions and are regulated by the hypothalamic–pituitary axis, they may share some common oncogenic molecular pathways. However, other risks factors, including medical interventions and hormones, are also observed to play a role. This article aims to provide a comprehensive review of the associations between the two cancers. The putative mechanisms, such as hormone alteration, autoimmune attack, genetic predisposition and other life-related factors are reviewed and discussed. Medical interventions, such as chemotherapy and radiotherapy, can also increase the risk of second primary cancers. This review will provide novel insights into the research designs, clinical managements and treatments of thyroid and breast cancer patients.

Cumulative consumption of tea is associated with lower risk of liver cancer: Updated results from the Shanghai Women's Health Study.

Prospective epidemiological studies have provided limited evidence for an association between tea consumption and liver cancer risk. Based on a population-based prospective cohort study in middle-aged Chinese women, we investigated the association between tea consumption and the risk of primary liver cancer. Detailed information on tea drinking habits and other potential confounders was obtained at the baseline interview. Incident liver cancer cases were identified through record linkage with the population-based cancer registry and verified through home visits and review of medical charts by medical experts. Multiple aspects of tea drinking habits including starting age, duration, intensity and cumulative consumption of any type of tea and green tea were considered. Multivariable-adjusted hazard ratios (aHRs) and their 95% confidence intervals (CIs) were derived from the Cox regression models. After a median follow-up time of 18.12 (interquartile range=1.59) years, 253 incident liver cancer cases were identified from 71 841 cohort members. Compared with never tea drinkers, the risk of liver cancer for participants who have consumed over 30 kg of dried tea leaves cumulatively was 0.56 (95% CI: 0.32-0.97). For those who drank green tea only, the aHR was 0.54 (95% CI: 0.30-0.98). This updated study suggested an inverse association between cumulative consumption of tea, especially green tea and the risk of primary liver cancer.

Postoperative radiotherapy might be a risk factor for second primary lung cancer: A population-based study.

BackgroundSurgery is the main curative therapeutic strategy for patients with initial primary lung cancer (IPLC). Most international guidelines recommend regular follow-ups after discharge to monitor patients for tumor recurrence and metastasis. As the overall survival (OS) in patients with lung cancer improves, their risk of secondary primary lung cancer (SPLC) increases. Previous studies on such patients lack separate assessment of different survival outcomes and evaluation of high-risk factors for SPLC. Therefore, we aimed to determine the correlation between high-risk factors and causes of death in patients with SPLC, based on the Surveillance, Epidemiology, and End Results (SEER) database.MethodsWe screened the SEER database for patients with IPLC and SPLC from 2004 to 2015 and included only patients who underwent surgery since the IPLC and in whom the cancer was pathologically verified of an International Classification of Diseases grade of 0-3 and to be non-small-cell lung cancer. The standardized incidence ratio (SIR) was calculated between variables and SPLC. Multivariable Cox proportional-hazards regression analyses were conducted to calculate the correlation of different variables with overall survival (OS) and cancer-specific survival (CSS). A competing-risk model was conducted for SPLC. The effect of baseline bias on survival outcomes by performing propensity score matching analysis in a 1: 6 ratio (SPLC: IPLC).ResultsFor patients aged 0-49 years, the overall SIR was higher in older patients, reaching a maximum of 27.74 in those aged 40-49 years, and at 11.63 in patients aged 50-59 years. The overall SIR was higher for patients who were more recently diagnosed with IPLC and increased with time after diagnosis. Male sex, SPLC (hazard ratio, 1.6173; 95% confidence interval, 1.5505-1.6869; P < 0.001), cancer grade III or IV, lower lobe of the lung, advanced stage and postoperative radiotherapy (PORT) were independently detrimental to OS. In terms of CSS, PORT was a high-risk factor.ConclusionsPostoperative radiotherapy is a risk factor for second primary lung cancer and detrimental to overall and cancer-specific survival in patients who had initial primary lung cancer. These data support the need for life-long follow-up of patients who undergo treatment for IPLC to screen for SPLC.

Amiodarone therapy and risk of primary lung cancer; insights from a real-life contemporary population study

Abstract Background Amiodarone is the most effective antiarrhythmic therapy to maintain sinus rhythm in atrial fibrillation (AF) patients. There is a controversy regarding the association of amiodarone therapy with an increased risk of lung cancer. We aimed to assess the relationship between amiodarone treatment and primary lung cancer (PLC) incidence in a contemporary population of AF patients. Methods This is a retrospective study among patients from the Southern district of Clalit Health Services in Israel between 1st January 1999 and 1st July 2021. The study population comprised solely of patients with atrial fibrillation since this is the most prevalent condition for prescribing amiodarone. Patients treated with amiodarone were matched in a 1:1 manner with controls not exposed to amiodarone based on age, sex, living area, and atrial fibrillation diagnosis duration. To avoid immortal time bias, follow-up times of the matched controls were left adjudicated to truncate the amiodarone-free period of their matched cases. Patients with prior PLC were excluded. The primary outcome was the incidence of any PLC. We performed survival analyses using multivariable Cox regression controlling for potential confounders. Results During the study period, 7,048 patients who initiated amiodarone treatment were identified, of whom 6,449 were matched with controls. The mean age was 71.5 years, and 46.4% were women among the matched population. The amiodarone-treatment group had higher rates of smoking (30.3% vs. 26.8%), prior non-lung-related malignancy (14.9% vs. 13.5%), rheumatic disease (4.5% vs. 3.5%), diabetes (38.3% vs. 32.6%), history of myocardial infarction (316% vs. 19.6%), renal failure (17.2% vs. 10.8%) and congestive heart failure (33.8% vs. 20.7%); p&amp;lt;0.05 for all. During the study, with a mean follow-up time of 5.7 years, PLC occurred in 94 (1.5%) patients in the amiodarone group and 79 (1.2%) patients in the control group [adjusted-hazard-ratio (aHR) 1.10 (confidence-interval 95% (CI95%, 0.78,1.55), p=0.6]. Factors independently associated with increased PLC risk were smoking [aHR 4.25 CI95% (3.01,5.99), p&amp;lt;0.001], non-lung-related malignancy [aHR 1.56, CI95% (1.00,2.42), p=0.050], and peripheral vascular disease [aHR 1.77, CI95% (1.16,2.71), p=0.008] Conclusion Chronic amiodarone treatment is not associated with increased risk for PLC. Smoking and prior non-lung-related malignancy and peripheral vascular disease were independently associated with increased PLC risk, suggesting that such patients should undergo closer surveillance for early detection of PLC. Funding Acknowledgement Type of funding sources: None.