Breast Cancer Research and Treatment最新文献

We read with great interest the recent article, "Comparison of survival between unilateral and bilateral breast cancers using propensity score matching: a retrospective single-center analysis" by Ozler et al. This study addresses an important gap in the literature by comparing disease-free survival (DFS) and overall survival (OS) between unilateral and bilateral breast cancer, and the use of propensity score matching (PSM) strengthens the validity of the findings. However, we would like to share several reflections that we believe can enhance the interpretation and future application of this research.

Purpose: The prognosis and optimal treatment for microinvasive breast cancer is controversial with some data indicating a higher local recurrence with microinvasive disease as compared to early-stage invasive breast cancer. The goal of our study was to compare long-term outcomes between patients with T1mi disease and early-stage breast cancer after breast-conserving surgery and whole breast irradiation (WBI).

Methods: We reviewed all patients treated at our institution from 2013 to 2019 with T1mi-T2N0 disease. Cox proportional hazard model was used to find independent prognostic variables associated with local recurrence (LR). Survival curves were analyzed by Kaplan-Meier.

Results: We found 1155 patients with 56 (4.8%) having T1mi disease. The 5-year local recurrence rate was 5.3% in patients with T1mi disease and 1.2% in patients T1-2 disease (HR = 2.73; 95% CI 0.43, 17.9; p = 0.09). On Cox multivariate analysis, younger age, positive margins and the need for re-excision were prognostic for LR. Out of the 3 patients with microinvasive disease who developed a local recurrence, two had DCIS < 2 mm from the margin and the third patient underwent two re-excisions due to DCIS margins < 2 mm.

Conclusions: Our study showed that patients with microinvasive disease treated with hypofractionated WBI had a numerically higher 5-year local recurrence rate than patients with T1a-2 disease though this difference was not statistically significant. Given the rarity of microinvasive disease, further work is needed to define optimal surgical and adjuvant management and to better clarify the risk of local recurrence in this patient population.

Purpose: To develop a novel simulation model for ductal carcinoma in situ (DCIS), fully validate it, and provide new estimates for DCIS in the setting of population-based biennial screening.

Methods: A micro-simulation Markov model for DCIS (SimDCIS) was developed. Input parameters were independently derived from the literature and transition parameters were age- and grade-dependent. The model was applied to the Dutch biennial screening program. SimDCIS was internally, cross, and externally validated by comparison of the model output to data from the Netherlands Cancer Registry, a modelling study on the United Kingdom Frequency Trial, and the United Kingdom screening program, respectively. Univariate and probabilistic sensitivity analyses were performed to estimate uncertainty. DCIS regression, progression to invasive breast cancer (IBC), clinical detection, and screen-detection were estimated in Dutch screening setting.

Results: SimDCIS matched observed data in internal, external, and cross-validation. The model was most sensitive to DCIS onset probability, and the maximum variation in screen-detection rate was 11%. In Dutch screening setting, DCIS regression, progression to IBC, clinical detection, and screen-detection were estimated at 8% (0-14%), 19% (16-24%), 8% (0-13%), and 61% (56-65%), respectively. Grade distribution was 20% grade 1, 38% grade 2, and 42% grade 3.

Conclusion: SimDCIS provides strong accuracy across validation methods and is particularly sensitive to DCIS onset probability. Most DCIS will be found through screening, of which less than 50% of DCIS will be grade 3, less than 1 in 10 will regress, and 1 out of 5 DCIS will progress to IBC in biennial screening setting.

Purpose: Evidence on the associations between categorical mammographic density and breast cancer risk by tumor invasiveness remains limited in Asian women. This large, population-based cohort study investigated the distribution of mammographic density by age and menopausal status, as well as its association with the risks of invasive breast cancer and ductal carcinoma in situ (DCIS) in South Korean women.

Methods: Mammographic screening was performed on 6,365,522 women between 2009 and 2014 through the Korean National Cancer Screening Program. Mammographic parenchymal composition was classified using the fourth edition of Breast Imaging Reporting and Data System. We computed multivariable-adjusted hazard ratios and 95% confidence intervals (CIs) using Cox proportional hazards regression models for the association between mammographic parenchymal composition and the risk of invasive cancer and DCIS.

Results: Overall, 40.6% of women had dense breasts, with the proportion decreasing with increasing age. A total of 44,468 incident breast cancer cases (0.7%) were documented. Compared with almost entirely fatty breasts, increasing mammographic density was associated with a higher risk of breast cancer (HR, 1.55; 95% CI 1.51-1.60 for scattered fibroglandular densities; HR, 2.14; 95% CI 2.08-2.21 for heterogeneously dense breasts; and HR, 2.59; 95% CI 2.50-2.69 for extremely dense breasts). Associations between mammographic density and breast cancer risk were similar for invasive cancer and DCIS, and did not vary significantly by menopausal status.

Conclusions: Mammographic density may be a significant risk factor for both invasive cancer and DCIS, regardless of menopausal status. It should be incorporated into breast cancer risk stratification and screening strategies.

Purpose: Patients with triple-negative breast cancer (TNBC) who have residual disease after neoadjuvant chemotherapy (NACT) benefit from adjuvant capecitabine. Older patients are not always treated according to guidelines, likely due to concerns regarding tolerance. We examined the use of adjuvant capecitabine, its association with outcomes, and subsequent emergency room visits (ER) and hospitalizations (HSP) among older patients with early-stage TNBC.

Methods: Retrospective, observational study using data in the SEER-Medicare database. Older patients (≥ 66 years) with early-stage TNBC, diagnosed in 2010-2019, who received NACT, underwent surgery, and were prescribed adjuvant capecitabine were included. We analyzed capecitabine use, its association with overall survival and breast-cancer specific survival, and time to first ER/HSP. Logistic regression, Kaplan-Meier estimates, and Cox regression models with propensity score adjustments were used.

Results: 239 of 1,799 older patients with TNBC received adjuvant capecitabine. Capecitabine use increased from 1.3% in 2010 to 29.6% in 2019. Older age, ≥ 71 years, (OR = 0.54, 95%CI 0.32-0.92) and ≥ 2 comorbidities (OR = 0.42, 95%CI 0.2-0.9) were associated with decreased odds of receiving ≥ 6 cycles of capecitabine. Increasing number of cycles of capecitabine was associated with decreased risks of death (HR = 0.74, 95%CI 0.66-0.83) and breast cancer-specific death (HR = 0.73, 95%CI 0.61-0.89). 55 patients (23%) treated with capecitabine experienced ER/HSP.

Conclusion: In recent years, adjuvant capecitabine is increasingly used for patients with early-stage TNBC. Patients with older age and more comorbidities received fewer cycles of capecitabine. While one-fourth of patients had ER/HSP, receipt of more cycles was associated with better survival.

Purpose: Tamoxifen undergoes metabolic activation by cytochrome P450 (CYP) enzymes to metabolites with more potent anti-estrogenic effects. Numerous studies demonstrate decreased tamoxifen efficacy associated with reduced CYP2D6 activity or lower Z-endoxifen concentrations. Women taking tamoxifen frequently experience vasomotor symptoms (VMS) that may require medical treatment. Many medications used for VMS or depression are CYP substrates that may reduce Z-endoxifen concentrations. While the drug-drug interactions (DDI) from potent CYP2D6 inhibitors (CYPi) on tamoxifen metabolism has been studied, the impact of less potent CYPi including drugs used to treat VMS remains largely unknown.

Methods: We performed a prospective trial to evaluate the impact of gabapentin or non-potent CYPi (venlafaxine citalopram) on plasma concentrations of tamoxifen and its metabolites (Z-endoxifen, N-desmethyl-tamoxifen (NDMT) and 4-hydroxy-tamoxifen (4HT).

Results: Patients enrolled were intermediate to extensive metabolizers by CYP2D6 genotyping. While tamoxifen and NDMT plasma concentrations were not significantly altered, the percent decrease in plasma Z-endoxifen concentration was statistically significant with the addition of venlafaxine (n = 22) or citalopram (n = 18) (median - 14.7 and - 14.4%, respectively) but not with gabapentin (n = 14) (median - 2.3%). A reduction in Z-endoxifen concentrations below the 5.9 ng/ml threshold associated with tamoxifen efficacy was observed in 12% of patients.

Conclusion: The addition of venlafaxine and citalopram but not gabapentin during tamoxifen treatment decreases plasma Z-endoxifen concentrations. SSRIs/SNRIs affecting tamoxifen biotransformation pathways, but with less potent CYPi potential, should be used cautiously in tamoxifen-treated patients and non-CYP inhibiting medications considered when possible.

Background: The risk of developing breast cancer up to age 80 for women with BRCA1/2 mutations is approximately 69-72%. The risk estimates, however, become labile in the later years of life. Many older BRCA1/2 mutation carriers who have not developed breast cancer continue to undergo high-risk surveillance. We evaluated breast cancers in women age ≥ 70 and identified which modality diagnosed the malignancy.

Methods: Females with BRCA1/2 mutations identified between 1996 and 2022 were included in this single institution retrospective review. The cohort was divided by age at BRCA1/2 diagnosis (30-59, 60-69 & ≥ 70). The number of malignancies and imaging modality which led to the diagnosis were recorded.

Results: There were 316 patients with BRCA1/2 mutations: 266/316 (84.2%) were 30-59 years old at the time of genetic testing, 35/316 (11.1%) were 60-69, and 15/316 (4.7%) were ≥ 70. Median follow-up was 57 months (IQR 21.6-114.6). There were 178 (56.3%) breast malignancies diagnosed; 161/266 (60.5%) age 30-59, 11/35 (31.4%) ages 60-69, and 6/15 (40%) age ≥ 70 (p = 0.002). Of patients with a malignant diagnosis (n = 178), 140/178 (78.7%) had their cancers discovered on either screening or diagnostic mammogram, 30/178 (16.9%) by MRI, 1 /178 (0.6%) on ultrasound, and 1/178 (0.6%) was discovered on surgical pathology. Of the breast cancers diagnosed in patients age ≥ 70, 66.7% (4/6) were found on mammogram.

Conclusions: In women ≥ 70 with BRCA1/2 mutations, mammograms may be sufficient surveillance. Given that a number of older BRCA1/2 carriers may never develop breast cancer, our data supports individualized care and consideration for de-escalated surveillance in those ≥ 70.

Purpose: Several variants in DNA damage response (DDR) genes increase the probability to develop breast cancer and show enrichment in Northern Finland. Here, the population prevalence and risk estimations were refined for sixteen recurrent pathogenic/likely pathogenic DDR gene variants.

Methods: Variant genotyping was performed in 2343 unselected Northern Finnish breast cancer cases and 4607 cancer-free controls, and tumor features and family history of cancer for the carriers were examined.

Results: Based on their prevalence and carrier family history, the studied BRCA1 and BRCA2 variants, PALB2 c.1592delT, and ATM c.7570G > C were confirmed as high-risk alleles, whereas CHEK2 c.1100delC, MCPH1 c.909_921del, and RAD50 c.687delT were moderate-risk alleles. FANCM c.5101C > T and c.5791C > T did not associate with overall breast cancer risk. Double carriers were significantly more common in cases (0.5%, 11/2343) than controls (0.07%, 3/4601, OR 7.2). The BRCA1/2 and PALB2 c.1592delT carrier tumors all had high proliferation rates, PALB2 c.1592delT associating also with grade 3 tumors (p = 0.002). Progesterone receptor (p < 0.05) and estrogen receptor positive tumors were enriched in ATM c.7570G > C and CHEK2 c.1100delC carriers, whereas MCPH1 c.904_916del carriers had a significantly high percentage of multifocal tumors (38%, p = 0.001). Moreover, one FANCM c.5101C > T homozygote case suffered severe side effects from chemotherapy.

Conclusion: The studied DDR gene variants were present in 9% of the unselected cases. As the presence of germline pathogenic variants can provide additional value for surgical decision-making and affect the choice of oncological treatments, the results promote the benefits of genetic testing as a part of breast cancer diagnostics.

Purpose: Somatostatin receptor (SSTR) expression has been reported in estrogen receptor-positive (ER +) metastatic breast cancer (mBC) by pathology and immunohistochemistry studies. We aimed to investigate whether SSTR could be a viable target for PET imaging and potential theranostics in ER + mBC.

Methods: Thirty prospectively recruited patients with ER + mBC underwent PET/CT imaging with [¹⁸F]FDG and [⁶⁸Ga]Ga-DOTATATE (within three weeks). Detection rates (per-patient, per-region), number of lesions detected, SUVmax values, Krenning scores, SSTR-FDG visual scores, and PET-based staging with both radiotracers were compared.

Results: [¹⁸F]FDG and [⁶⁸Ga]Ga-DOTATATE PET/CT had similar per-patient detection rates (100% vs 96.7%, P = 1.0). Per-region and per-lesion analyses revealed comparable detection of local/breast lesions, nodal, and skeletal metastases. However, [¹⁸F]FDG outperformed [⁶⁸Ga]Ga-DOTATATE in detecting visceral/other metastases (235 vs 128 lesions, P = 0.003). [⁶⁸Ga]Ga-DOTATATE resulted in a lower PET-based M-stage compared to [¹⁸F]FDG in 10% of patients, although T-/N-stages were concordant in all patients. HER2- patients showed a trend of higher [⁶⁸Ga]Ga-DOTATATE lesional SUVmax values compared to the HER2 + sub-group (median 9.0 vs 3.8, P = 0.078). 3/30 (10%) participants had a patient-level Krenning score ≥ 3 ([⁶⁸Ga]Ga-DOTATATE uptake higher than liver background in majority of the lesions), potentially making them suitable for SSTR-targeted radionuclide therapy.

Conclusions: SSTR-targeted theranostics may represent a novel potential alternative in a subset of patients with ER + mBC. Its generalized applicability is limited by poor sensitivity for visceral metastases and significant inter-lesion heterogeneity. Future studies must identify how tumor subtype, proliferation, and prior systemic therapies impact SSTR expression levels in these patients to ensure meaningful clinical translation.

Clinical trial registration: Clinical Trials Registry-India: CTRI/2023/03/051025 (prospectively registered on 23.03.2023).

Introduction: NCCN recommendations suggest irradiating chest wall/breast only + regional node irradiation (RNI) of the undissected axillary levels for node-positive breast cancer (BC) patients. We retrospectively analyzed a cohort of node-positive BC patients who received adjuvant radiotherapy (RT) with a volume de-escalation at the level of axillary nodes.

Material and methods: We conducted a retrospective analysis of node-positive BC patients treated with adjuvant RT administered following a conventional fractionation schedule using a 3D-conformal technique to the chest wall or breast and only the IV axillary level. The primary endpoint of the study was disease free survival (DFS). Secondary endpoints included loco-regional control (LRC), and Overall Survival (OS). Toxicity was documented according to the Radiation Therapy Oncology Group (RTOG) criteria.

Results: A total cohort of 343 patients was analyzed. Loco-regional recurrence occurred in 100 (29.1%). The 5- and 10-year Kaplan-Meyer curves for DFS were 81.4% (95% CI: 79.3%-83.5%) and 60.9% (95% CI: 57.6%-64.5%), respectively. Multivariate Cox analysis confirmed that lymph node ratio (HR = 9.76, 95% CI: 3.12-30.53, p = 0.0001), Luminal B subtype (HR = 2.03, 95% CI: 1.26-3.29, p = 0.004), and triple-negative subtype (HR = 2.70, 95% CI: 1.22-5.99, p = 0.01) were significant predictors of poor DFS. Lymphedema in the ipsilateral arm was reported in 32 (9.3%) patients, primarily Grade 1 or 2.

Conclusions: Improved patients' selection and a broader use of systemic therapy could make de-escalation a feasible option. However, this approach should be avoided in patients with extensive nodal involvement, specific molecular subtypes, or comorbidities that prevent the use of chemotherapy.