Small Invasive Breast Cancers Research Articles

Prognostic Value of PCSK9 Levels in Premenopausal Women at Risk of Breast Cancer-Evidence from a 17-Year Follow-Up Study.

The involvement of cholesterol in cancer development remains a topic of debate, and its association with breast cancer has yet to be consistently demonstrated. Considering that circulating cholesterol levels depend on several concomitant processes, we tested the liability of plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), one of the key regulators of cholesterol levels, as a prognostic biomarker in the context of breast neoplastic events. Within a prospective randomized breast cancer prevention trial we measured baseline plasma levels of PCSK9. A total of 235 at-risk premenopausal women were randomized and followed up for 17 years. Participants enrolled in this placebo-controlled, phase II, double-blind trial were randomly assigned to receive either tamoxifen 5 mg/d or fenretinide 200 mg/d, both agents, or placebo for 2 years. The associations with breast cancer events were evaluated through competing risk and Cox regression survival models, adjusted for randomization strata (5-year Gail risk ≥ 1.3% vs. intraepithelial neoplasia or small invasive breast cancer of favorable prognosis), age, and treatment allocation. PCSK9 associations with biomarkers linked to breast cancer risk were assessed on blood samples collected at baseline. The plasmatic PCSK9 median and interquartile range were 207 ng/mL and 170-252 ng/mL, respectively. Over a median follow-up period of 17 years and 89 breast neoplastic events, disease-free survival curves showed a hazard ratio of 1.002 (95% CI: 0.999-1.005, p = 0.22) for women with PCSK9 plasma levels ≥ 207 ng/mL compared to women with levels below 207 ng/mL. No differences between randomization strata were observed. We found a negative correlation between PCSK9 and estradiol (r = -0.305), maintained even after partial adjustment for BMI and age (r = -0.287). Cholesterol (r = 0.266), LDL-C (r = 0.207), non-HDL-C (r = 0.246), remnant cholesterol (r = 0.233), and triglycerides (r = 0.233) also correlated with PCSK9. In premenopausal women at risk of early-stage breast cancer, PCSK9 did not appear to have a role as a prognostic biomarker of breast neoplastic events. Larger studies are warranted investigating patients in different settings.

Vacuum-assisted excision of small breast cancers under ultrasound guidance

PurposeThe purpose of this study was to evaluate if it is possible to completely remove small breast cancer tumours with vacuum-assisted excision (VAE) under ultrasound guidance. MethodsWomen ≥ 50 years old with a biopsy proven invasive cancer ≤ 10 mm were selected between October 2021 and November 2021 based on referrals and enrolled in this prospective study. The patients underwent VAE within six weeks following biopsy to remove the tumour. After the tumour was excised and the biopsy cavities margins were shaved, a radioactive seed was inserted into the biopsy cavity. The VAE excision cavity and surrounding tissue were surgically excised. Preliminary VAE results were evaluated after ten patients. For the study to proceed at least 80 % of the breast cancer tumours had to be completely removed by VAE. ResultsThe tumours median size in mammography was 8.5 mm (6–9 mm) and in ultrasound 6.5 mm (4–9 mm). The shape of the lesion was round in three (30 %), oval in two (20 %) and irregular in five (50 %) patients. None of the tumours were completely removed in the first VAE specimen, meaning that there was invasive cancer or ductal carcinoma in situ (DCIS) in the “shaved margins” and/or the surgical specimen. In five (50 %) cases, the surgical specimen was free of invasive cancer and DCIS. ConclusionsNone of the small invasive breast cancers were completely excised with VAE under ultrasound guidance, therefore it is not a reliable method to remove small breast cancers.

Countercurrents: DCIS or Cancer? Why All the Confusion?

At present, women with ductal carcinoma in situ are counseled that they have a pre-malignant condition which carries the possibility of progression to a fully malignant breast cancer. However, in most cases, the treatment of DCIS resembles that of a small invasive breast cancer and this is a source of confusion to many. In order to properly evaluate the benefit of radiotherapy, mastectomy and contralateral mastectomy, it is necessary to consider the risks of ipsilateral invasive cancer and of contralateral breast cancer in women with DCIS and with small invasive breast cancer. Several registry-based studies indicate that the risks of ipsilateral and contralateral cancer are similar in the two conditions and therefore a similar approach to treatment is rational.

Prognostic Value of Stromal Type IV Collagen Expression in Small Invasive Breast Cancers.

Breast cancer is the most common cause of cancer death among women worldwide. Localized breast cancer can be cured by surgery and adjuvant therapy, but mortality remains high for tumors that metastasize early. Type IV collagen is a basement membrane protein, and breach of this extracellular matrix structure is the first step of cancer invasion. Type IV collagen is found in the stroma of many cancers, but its role in tumor biology is unclear. Here, expression of type IV collagen in the stroma of small breast cancers was analyzed, correlated to clinically used prognostic biomarkers and patient survival. The findings were further validated in an independent gene expression data cohort. Tissue samples from 1,379 women with in situ and small invasive breast cancers (≤15 mm) diagnosed in 1986-2004 were included. Primary tumor tissue was collected into tissue microarrays. Type IV collagen expression in tissues was visualized using immunohistochemistry. Gene expression data was extracted from the Cancer Genome Atlas database. Out of 1,379 women, 856 had an invasive breast cancer and type IV collagen staining was available for 714 patients. In Kaplan-Meier analysis high type IV collagen expression was significantly associated (p = 0.026) with poorer breast cancer specific survival. There was no correlation of type IV collagen expression to clinically used prognostic biomarkers. High type IV collagen expression was clearly associated to distant metastasis (p = 0.002). In an external validation cohort (n = 1,104), high type IV collagen mRNA expression was significantly (p = 0.041) associated with poorer overall survival, with overexpression of type IV collagen mRNA in metastatic tissue. Stromal type IV collagen expression in the primary tumor correlates to poor breast cancer specific survival most likely due to a higher risk of developing distant metastasis. This ECM protein may function as biomarker to predict the risk of future metastatic disease in patients with breast cancers.

A comparison of local therapy alone with local plus systemic therapy for stage I pT1aN0M0 HER2+ breast cancer: A National Cancer Database analysis.

Small invasive breast cancers (BCs) with tumor sizes ≤5 mm (T1a) are associated with an excellent prognosis without systemic therapy. Although HER2 overexpression (HER2+) is associated with a higher risk of recurrence and poorer clinical outcomes, in the absence of HER2 directed therapy, it remains unclear whether adjuvant systemic therapy is necessary in node-negative patients diagnosed with HER2+ invasive BCs ≤5 mm (pT1aN0M0). The National Cancer Database was searched to identify patients diagnosed with HER2+ pT1aN0M0 BCs from 2004 to 2017. The cohort was stratified by treatment status: local therapy alone or local plus adjuvant systemic therapy. A 1:1 propensity match was performed. Overall survival (OS) was analyzed using stratified multivariable Cox proportional hazards regression analyses. Of the 8948 patients found, 4026 (45.0%) underwent surgery alone, and 4922 (55.0%) received surgery plus systemic therapy. Patients with either moderately differentiated (odds ratio [OR], 2.053; P < .001) or poorly/undifferentiated tumors (OR, 3.780; P < .001) or with the presence of lymphovascular invasion (OR, 3.351; P < .001) were more likely to have received systemic therapy. Propensity matching generated 1162 pairs of patients who were hormone receptor positive (HR+) and 748 pairs who were hormone receptor negative (HR-). Propensity matching effectively reduced selection bias between study groups. In the matched cohort, the addition of systemic therapy was not associated with superior OS (hazard ratio for HR+, 1.613; P = .107, and hazard ratio for HR- 1.319; P = .369) compared with patients who received local therapy alone. In pT1aN0M0 HER2+ BC, the addition of adjuvant systemic therapy after surgical excision was not associated with improved OS compared with local therapy alone.

127 Poster - Breast Lesion Excision System as a treatment method for small invasive breast cancers

127 Poster - Breast Lesion Excision System as a treatment method for small invasive breast cancers

Precision Science on Incidence and Progression of Early-Detected Small Breast Invasive Cancers by Mammographic Features.

The aim was to evaluate how the inter-screening interval affected the performance of screening by mammographic appearances. This was a Swedish retrospective screening cohort study with information on screening history and mammography features in two periods (1977–1985 and 1996–2010). The pre-clinical incidence and the mean sojourn time (MST) for small breast cancer allowing for sensitivity by mammographic appearances were estimated. The percentage of interval cancer against background incidence (I/E ratio) was used to assess the performance of mammography screening by different inter-screening intervals. The sensitivity-adjusted MSTs (in years) were heterogeneous with mammographic features, being longer for powdery and crushed stone-like calcifications (4.26, (95% CI, 3.50–5.26)) and stellate masses (3.76, (95% CI, 3.15–4.53)) but shorter for circular masses (2.65, (95% CI, 2.06–3.55)) in 1996–2010. The similar trends, albeit longer MSTs, were also noted in 1977–1985. The I/E ratios for the stellate type were 23% and 32% for biennial and triennial screening, respectively. The corresponding figures were 32% and 43% for the circular type and 21% and 29% for powdery and crushed stone-like calcifications, respectively. Mammography-featured progressions of small invasive breast cancer provides a new insight into personalized quality assurance, surveillance, treatment and therapy of early-detected breast cancer.

Screening Breast Ultrasound: Update After 10 Years of Breast Density Notification Laws.

OBJECTIVE. Breast density notification laws have grown from the first state legislation in Connecticut in 2009 to a federally mandated update to the Mammography Quality Standards Act in 2019. CONCLUSION. The increasing recognition of limited mammographic sensitivity in women with dense breasts has led to greater utilization of supplemental screening ultrasound. Robust data support improved detection of small node-negative invasive breast cancers with adjunctive ultrasound. Digital breast tomosynthesis and other emerging modalities may also play a role in screening guidelines.

Cryosurgery for primary breast cancers, its biological impact, and clinical outcomes.

Recently, a number of new minimally invasive image-guided percutaneous ablation treatments, including cryoablation, radiofrequency ablation, microwave ablation, high-intensity focused ultrasound, laser ablation, and irreversible electroporation have been developed. Several studies have shown the feasibility and safety of these cryoablation therapies for the treatment of benign breast tumors and small invasive breast cancer. Although the complete response rate of cryoablation for breast cancer is reported to be relatively good, most studies enrolled a small number of patients, and so reliable conclusions could not be drawn. In this review, we introduce the mechanisms of action of cryoablation, and summarize the current literature on the efficacy and safety of cryoablation for breast cancer. Cryoablation also induces an immunomodulatory effect, which is an interesting topic of research in the era of immune checkpoint inhibitors. Cryoablation for primary tumor may enhance the treatment effect of immune checkpoint inhibitors in patients with breast cancer. Further investigations of this new therapeutic strategy are needed.

A comparison of two models for breast cancer mortality for women with ductal carcinoma in situ: an SEER-based analysis.

Approximately 1% of patients with ductal carcinoma in situ (DCIS) will die of breast cancer within 10years. Women who develop an invasive breast cancer after DCIS have a much greater risk of dying than those who do not and it is often stated that these deaths are a consequence of metastases from the invasive in-breast recurrence. This progression is the result of a two-step process: first local invasive recurrence and then spread beyond the breast. A large proportion of women who die of DCIS have no record of invasive recurrence. We used SEER data and a simulation approach to test whether the actual mortality data are consistent with the two-step model. First, we constructed Kaplan-Meier mortality curves for all patients with pure DCIS and with small node-negative invasive breast cancers in the Surveillance, Epidemiology and End Results (SEER) registries database (1998-2014). We then constructed, through simulation, theoretical breast cancer mortality curves. To model the two-step scenario, we applied the annual incidence rates of incident invasive cancer following DCIS and of death from invasive cancer after DCIS to a theoretical cohort of 100,000 women. The observed 15-year breast cancer-specific mortality rate for patients with pure DCIS in the SEER database was 2.0%. The expected mortality for DCIS patients (assuming a two-step process) was only 1.1% at 15years. Assuming the mortality rates following DCIS were one-half of those observed for patients with small invasive breast cancers, the expected mortality at 15years post-DCIS was 2.1%. In the SEER database, we observed far more deaths from DCIS than would be expected under a model where all deaths from breast cancer occur amongst women who experience an invasive local recurrence. This lends support to the hypothesis that DCIS mortality is not restricted to those women who experience an in-breast invasive cancer and that DCIS has properties similar to small invasive breast cancers.

Impact of microinvasion on breast cancer mortality in women with ductal carcinoma in situ.

Ductal carcinoma in situ (DCIS) is a neoplastic proliferation of epithelial cells which is confined within the basement membrane of the mammary ductal-lobular system. It is of interest to determine to what extent the potential to metastasize increases for DCIS patients when the basement membrane is breached (i.e. microinvasion is present). We retrieved the records of 525,395 women who had either first primary DCIS or small (≤2.0cm) node-negative invasive breast cancer in the Surveillance, Epidemiology and End Results (SEER) registries database (1990-2013). For each patient, we extracted information on year of diagnosis, age at diagnosis, tumour size, tumour grade, oestrogen receptor status, use of radiotherapy, type of surgery, cause of death and follow-up time. We classified patients into four groups, according to the size of the invasive component of the primary tumour. We estimated the actuarial rate of breast cancer-specific mortality at ten and 20years for women in each size category. We identified 161,394 women with pure DCIS, 13,489 women with microinvasive carcinoma (≤0.1cm of invasion), 153,856 women with invasive cancer 0.2-1.0cm in size and 196,656 women with invasive cancer 1.1-2.0cm in size. The 20-year actuarial breast cancer-specific mortality rate was 3.8% for women with pure DCIS, was 6.9% for women with microinvasive carcinoma, was 6.8% for women with invasive cancer 0.2-1.0cm in size and was 12.1% for women with invasive cancer 1.1-2.0cm in size. The adjusted hazard ratio for death associated with microinvasive carcinoma (vs. pure DCIS) was 2.00 (95% CI 1.76-2.26; p<0.0001). In terms of prognosis, microinvasive cancer more closely resembles small invasive cancer 0.2-1.0cm) than pure DCIS. For invasive cancers under 1.0cm, size has little impact on mortality.

Pathobiology of HER 2 positive small invasive (T1a,b) breast cancer: “A wolf in sheep’s clothing”

Small invasive breast cancers (cancers with maximum diameter <1cm, T1a,b) become more prevalent form of breast cancer as a result of the introduction of breast cancer mammographic screening programs. Although associated with an excellent prognosis, T1a,b breast cancers are heterogeneous group of tumors with prognostically unfavorable subset of cases, primarily those with axillary lymph node metastases. To determine if the HER2 overexpression is associated with the prognostically unfavorable traditional clinicopathological features in this group of breast cancers, clinicopathological features (age, tumor size, histological type, histological grade, nodal status, hormone receptor status, proliferation index, lymphovascular invasion, ploidy) of 38 HER2 positive T1a,b cancers were compared with those of the control group consisting of 315 HER2 negative T1a,b cancers. The comparison of clinicopathological features was made using χ2 and t-test. HER2 positive T1a,b breast cancers were significantly associated with higher tumor grades (p<0.001), negative hormone receptors (p=0.008), presence of lymphovascular invasion (p=0.025), high proliferation index (p<0.001), and abnormal DNA content (p=0.04). We also noticed the higher frequency of lymph node positive cases in the HER2 positive group of cancers (p=0.05). There were no differences in age, tumor size and histological type between investigated groups. Our group of HER2 positive T1a,b breast cancers was associated with many unfavorable traditional prognostic factors, demonstrating that this subtype of early breast cancer has an aggressive biological phenotype which may have potential benefit from adjuvant chemo and immunotherapy.

Nipple sparing mastectomy for breast cancer is associated with high patient satisfaction and safe oncological outcomes

BackgroundThe preservation of the nipple areolar complex (NAC) for cancer treatment is still a matter of debate because of suspected increase of local recurrence and surgery-specific complications. The aim of the study was to investigate both the relapse risk associated with nipple sparing mastectomy (NSM) for breast cancer and women's satisfaction with preservation of the NAC. MethodsWe included retrospectively all patients who had skin-sparing mastectomy (SSM) or NSM from 2007 to 2012 for breast cancer or ductal carcinoma in situ (DCIS). We compared NSM and SSM group for oncological and surgical outcomes. Patients’ satisfaction and quality of life has been evaluated by a specifically designed questionnaire. ResultsWe included 63NSM (41.5%) and 89SM (58.5%). Eighty-nine (58.6%) patients had DCIS, and the other had small invasive disease. Median follow-up was 42 (IQR: 18–58) months. Local recurrence rate was 1.7% (n=1) in the NSM group and 0% in the SSM group without recurrence in the preserved nipple. After NSM, one patient had complete NAC necrosis, and three patients suffered partial necrosis. Satisfaction with the NAC was higher in the NSM group compared to the SSM group with delayed reconstruction of the nipple (75% vs. 59%, P=0.14). Patients with NSM required less psychological support before (P=0.028) and immediately after surgery (P=0.14) than patients in the SSM group. ConclusionNSM can successfully and safely be performed for pre-invasive and small invasive breast cancer. Besides esthetic aspects, preserving the nipple may ease the acceptance of these radical form of surgery.

Abstract P2-13-09: Is nipple-sparing mastectomy with implant reconstruction for breast cancer safe and worthwhile?

Abstract Background: Nipple-sparing mastectomy (NSM) is a standard for bilateral prophylactic surgeries. However for cancer treatment, the preservation of the nipple areolar complex (NAC) is still discussed because of suspected increase of local recurrence and surgical specific complications as nipple or mastectomy flap necrosis. The aim of the study was to investigate both the relapse risk associated with NSM for breast cancer and women's satisfaction with preservation of the NAC. Methods: We included retrospectively all patients who had skin-sparing mastectomy (SSM) or NSM from 2007 to 2012 for breast cancer or ductal carcinoma in situ (DCIS). We compared NSM and SSM group for oncological (overall survival (OS) and disease-free survival (DFS)) and surgical outcomes. Patients' satisfaction and quality of life has been evaluated by a specifically designed questionnaire, addressed by mail and inspired by the Breast-Q questionnaire with specific assessment of global esthetic result, harmony with the native breast and need for psychological support. Results: During the study, we operated 5600 patients for a breast cancer, among them, 152 had NSM (n=63 / 41.5%) or SSM (n=89 / 58.5%) with immediate implant breast reconstruction. Eighty-nine (58.6%) patients had DCIS, and the other had invasive disease (86.9% of T1). The mastectomy has been indicated for primary cancer (81%) or recurrence (19%). The two groups did not differ significantly according to histological type (p=0.10), grade (p=0.84), hormonal receptor (p=0.7), HER2 (p=1.00), Ki67 (p=0.75) or node metastases (p=0.64). Median follow-up was 42 (IQR: 18-58 ) months. No cancer-related death occurred during the study. Local recurrence rate was 1.7% (n=1) in NSM group and 0% in SSM group (p=0.35). The recurrence did not appear on the preserved nipple. Severe complication requiring surgery (Grade 3 of Clavien-Dindo classification) occurred in 9.9% of the cases. In the NSM group, one patient had complete NAC necrosis and three patients suffered partial necrosis. Severe skin-flap necrosis leading to implant removal was more frequent in the SSM group (SSM: 6.7% (n=6) ; NSM: 0% (n=0); p=0.042). One hundred and four (80%) patients answered the questionnaire. Satisfaction about the aspect of the NAC was higher in the NSM group compared to SSM with delayed reconstruction of the nipple (75% vs 59%, p=0.14). Patients with NSM needed less psychological support before (p=0.028) and immediately after surgery (p=0.14) than patients in the SSM group, which may suggest a better acceptation of the surgery in this group. Conclusion: NSM for breast cancer surgery was not associated with significant increase of local recurrence rate or surgical complications. Patient's satisfaction was high. Therefore, nipple-sparing mastectomy with immediate implant reconstruction can successfully and safely be performed for pre-invasive and small invasive breast cancer. Besides esthetic aspects, preserving the nipple may ease the acceptation of these radical surgeries. Citation Format: Regis C, Mesdag V, Tresch E, Chauvet MP, Boulanger L, Collinet P, Giard S. Is nipple-sparing mastectomy with implant reconstruction for breast cancer safe and worthwhile?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-13-09.

Abstract P2-03-01: Are all small tumors low risk? Characterization of small invasive node negative breast cancers (BC) enrolled in the EORTC 10041/BIG 3-04 (MINDACT) trial

Abstract Background: Adjuvant systemic therapy for subcentimetric N0 BC is controversial. These tumors have good prognosis, but a subgroup has high risk of relapse and requires adjuvant therapy. The best tool to identify this subgroup is unknown. We clinically and biologically characterize pT1abN0M0 tumors from patients enrolled in MINDACT.Patients and Methods: All MINDACT pts with pT1abN0 tumors were included. Descriptive statistical analysis included age, menopausal status, centrally assessed tumor grade, Ki67, ER, PR and HER-2 status. Cut-off value for high Ki67 was 20%. IHC subtypes are per 2013 St. Gallen consensus/ ESMO guidelines. Genomic tests (Mammaprint, Targetprint, BluePrint) were performed and their concordance rate with central pathology evaluated. We report clinical (modified version of adjuvant online!) and genomic risk assessment (MammaPrint) for these patients. Survival data will be reported after MINDACT primary analysis.Results:826 patients with T1abN0 tumors were enrolled in MINDACT, [12.3% of all patients (6694) and 16% of all N0 tumors];310 (35%) patients were ≥ 60 years and 537 (65%) were postmenopausal. Most (710;86%) samples were tested by central pathology. Tumors were mainly ductal (579;81.5%), ER + (650;91.5%), and PR+ (593;83.5%);44(6.2%)were HER-2 +; 520 (73.2%) had a low Ki67&amp;174 (24.5%) had high Ki-67 labeling index; 80 (11.3%) were grade 3 &amp; 328 (46.2%) grade 2 tumors. According to Targetprint, 761/826 (92.1%) tumors were ER+; 624/826 (75.5%) PR+; 45/826 (5.4%) HER2+. Concordance between Targetprint and central pathology was higher for ER (kappa= 0.90) and lower for PR and HER2 (kappa=0.60 and 0.73 resp).Molecular subtype classification by IHC surrogates showed 420/710 (59.2%) Luminal A tumors; 189/710 (26.6%) Luminal B; 36/710 (5.1%) Luminal B/ HER2+; 8/710 tumors (1.1%) HER-2 + and 37/710 (5.2%) TNBC. Using BluePrint 739/826 (89.5%) were Luminal; 29/826 (3.5%) HER-2 + and 58/826 (7.0%) basal. Combining BluePrint and MammaPrint 609/826 (73.7%) tumors were Luminal A&amp;129/826 (15.6%) Luminal B. Agreement between Mammaprint and Ki67 for distinction of luminal A vs B/HER-2 neg. tumors was low (kappa=0.31), similar to the overall MINDACT results (kappa=0.35).Using clinical risk assessment 820/826 (99.3%) were low-risk (CL). Using genomic risk assessment 624/826 (75.5%) were low risk (GL) and 201/826 (24.3%) were high-risk (GH). Overall, 624/826 (75.5%) were both CL/GL and 196/826 (23.7%) were CL/GH. The percentage of discordant CL/GH cases among T1abN0 tumors (196/826, 23.7%) is higher than in all MINDACT cohort (592/6694, 8.9%) and among T1c-2-3N0 tumors (381/4462, 8.5%). T1ab tumors were mainly 720/826 (87.2%) treated with BCS and radiotherapy; adjuvant treatment and compliance rate will be available at the meeting. Conclusions:1) Results show biological characteristics are relevant for T1abN0 BC&amp; that size/nodal status could be insufficient determinants of adjuvant systemic therapy. 2) A significant portion (23.7%) of such tumors, clinically classified as low risk, was genomically high risk by MammaPrint.3) IHC surrogates don't always accurately reflect genomic molecular subtyping. Citation Format: Giuseppe Viale, Femke Snoo, Laura Van't Veer, Emiel Rutgers, Martine Piccart, Jan Bogaerts, Fatima Cardoso, Konstantinos Tryfonidis, Leen Slaets. Are all small tumors low risk? Characterization of small invasive node negative breast cancers (BC) enrolled in the EORTC 10041/BIG 3-04 (MINDACT) trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-03-01.

Molecular markers as prognostic factors in DCIS and small invasive breast cancers

Molecular markers as prognostic factors in DCIS and small invasive breast cancers

Molecular Markers as Prognostic Factors in DCIS and Small Invasive Breast Cancers.

Ductal carcinoma in situ (DCIS) accounts for up to half of screen-detected breast cancers and thus constitutes a major public health problem. Despite effective current treatment many patients with DCIS are either over- or undertreated because of the paucity of precise models to predict recurrence or progression. The combination of clinical and molecular factors as already applied for invasive disease may help to build such models also for DCIS. We compared 53 DCIS (36.6 %) and 92 (63.4 %) invasive breast cancer cases and found no significant differences in age, receptor status of ER, PR, and HER2, and the use of radiotherapy. Interestingly, the proportion of disseminated tumor cells (DTC) did also not significantly differ between DCIS and invasive cases (p = 0.57). A negative PR status was associated with the detection of DTCs (p = 0.026). We then compared relationships of clinical parameters and biomarkers with patients' prognosis in 43 DCIS and 40 small invasive tumors ≤ 5 mm (T1a). ER negativity was associated with shorter relapse free survival in the complete cohort (p = 0.004) and showed a trend in both subgroups (p = 0.053 for DCIS and p = 0.046 for T1a, respectively). In conclusion, we found markedly similar properties of both DCIS and small invasive breast cancers with respect to the distribution of several parameters as well as to the prognostic value of biomarkers. DCIS with a luminal phenotype seem to be characterized by a favourable prognosis.

Shear-wave elastography contributes to accurate tumour size estimation when assessing small breast cancers

To assess whether the size of peritumoural stiffness (PTS) on shear-wave elastography (SWE) for small primary breast cancers (≤15mm) was associated with size discrepancies between grey-scale ultrasound (GSUS) and final histological size and whether the addition of PTS size to GSUS size might result in more accurate tumour size estimation when compared to final histological size. A retrospective analysis of 86 consecutive patients between August 2011 and February 2013 who underwent breast-conserving surgery for tumours of size ≤15mm at ultrasound was carried out. The size of PTS stiffness was compared to mean GSUS size, mean histological size, and the extent of size discrepancy between GSUS and histology. PTS size and GSUS were combined and compared to the final histological size. PTS of >3mm was associated with a larger mean final histological size (16 versus 11.3mm, p<0.001). PTS size of >3mm was associated with a higher frequency of underestimation of final histological size by GSUS of >5mm (63% versus 18%, p<0.001). The combination of PTS and GSUS size led to accurate estimation of the final histological size (p=0.03). The size of PTS was not associated with margin involvement (p=0.27). PTS extending beyond 3mm from the grey-scale abnormality is significantly associated with underestimation of tumour size of >5mm for small invasive breast cancers. Taking into account the size of PTS also led to accurate estimation of the final histological size. Further studies are required to assess the relationship of the extent of SWE stiffness and margin status.

Abstract P1-01-26: The feasibility of SNIPE trial; sentinel lymph node biopsy vs. no-SLNB In patients with early breast cancer

Abstract Background: The results of ZOO11 have shaken our longstanding approach for the axillary management of small invasive breast cancers where the incidence and burden of axillary metastasis would be much less than that of ZOO11 population. The traditional approach of sentinel lymph node biopsy (SLNB) for ‘‘all invasive cancers’’ is challenged due to the diminishing role of axillary lymph nodes (ALNs) status in guiding adjuvant systemic therapy. Certainly this raises the question of whether SLNB can be avoided in a select group of patients without compromising clinical outcomes? The aim was to identify a group of patients with a very low burden of axillary disease where SLNB is no longer required. The feasibility of the proposed SNIPE trial; Sentinel lymph node biopsy vs. No-SLNB In Patients with Early breast cancer was discussed and compared with SOUND trial, Sentinel node vs. Observation after axillary UltrasouND. Method: Patients with breast cancers ≤ 2 cm in size, clinically node negative who underwent breast conserving surgery and SLNB were identified. Patients were divided into different groups according to clinicopathological variables. The incidence of ALNs metastasis, further non-SLNs metastasis and ≥ 4 total number of tumour positive ALNs were determined. Results:194 patients met the inclusion criteria. The mean patient age was 58.5 y;75% were ≥ 50 y. The incidence of tumour positive ALNs is &amp;lt; 5% in T1b, G1-2 tumours where SLNB could be omitted without compromising the surgical outcomes. The burden of axillary nodal disease is shown below: Incidence and burden of axillary metastasis in different groups.GroupsT1 tumours(SOUND trial)T1, G1-2T1b tumoursT1b, G1-2(SNIPE trial)T1 and G1≤ 15mm G1-2≤ 15mm G1Total patients with T1 tumours and clinically negative axilla with no multifocality of tumour = 194Number of patients1941514943579243Incidence of ALNs mets30/194(15.5%)20/151(13.3%)6/49(12.4%)4/43(9.3%)8/57(14%)15/92(16.3%)7/43(16.3%)Incidence of ALNs mets excluding micromets13.4%11.9%6.1%4.6%10.5%13%11.6%OSM (Overall size of metastasis) mean, median, range.4.1,3(0.3-19)3.7,3(0.3-9)3.5,1.9(0.3-9)3.5,3(0.3-9)3.7,3(0.3-9)3.7,3(0.3-9)3.7,3(0.3-9)Incidence of non-SLNs metastasis9/30(30%)7/20(35%)1/6(16.7%)0%2/8(25%)3/15(20%)2/7(28.6%)Incidence of ≥ 4 total number of tumour positive ALNs5/194(2.5%)4/151(2.6%)1/49(2%)0%1/57(1.7%)1/92(1.1%)1/43(2.3%) Conclusion: It is possible to identify a group of patients where burden of axillary disease is acceptably low enough that SLNB can be avoided. Feasibility of a non-inferiority, multi-centres Randomized Controlled Trial in a select group of patients with or without SLNB has been explored to compare the distant disease free, disease free and overall survival and axillary relapse rate. Patients with 2 ≤ tumour positive SLNs would not have axillary node dissection inline with the recommendations of ZOO 11 trial. Overall, 1600 patients would be required to show that the group without SLNB is no more inferior in the outcomes to that with SLNB. Inclusion criteria and management of tumor positive SLNs in this proposed trial is open to discussion and should be debated intensively before starting such an important trial which may also improve accrual for this trial. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-26.

The feasibility of a randomised controlled trial for the axillary management of a select group of invasive breast cancer patients: SLNB vs. no-SLNB

The results of ZOO11 have shaken our thinking and approach for the axillary management of small invasive breast cancers where the incidence and burden of axillary metastasis would be much less than that of ZOO11 population. The traditional approach of sentinel lymph node biopsy (SLNB) for "all invasive cancers" is challenged because of the diminishing role of axillary lymph nodes (ALNs) status in guiding the adjuvant systemic therapy. Certainly this raises the question of whether SLNB can be avoided in a select group of patients without compromising clinical outcomes. The aim of this study was to identify such a group of patients in whom SLNB is no longer required. Patients with breast cancers ≤2 cm in size and clinically negative axilla who underwent breast conserving surgery (BCS) and SLNB were identified. Patients were divided into different groups; incidence of ALNs metastasis, further non-SLNs metastasis and a total number of tumour positive ALNs of ≥4 were determined. A total of 194 patients met the criteria; incidence of tumour positive SLNs, further non-SLNs metastasis and a total number of tumour positive ALNs of ≥4 varied between different groups and was 9.3-15.5 %, 0-35 % and 0-2.6 %, respectively. Patients with T1b, grade 1-2 tumours had less than 5 % risk of ALNs macrometastasis. It is possible to identify a group of patients whose burden of axillary disease is acceptably low enough that SLNB can be avoided. Feasibility of a non-inferiority randomised controlled trial (RCT) in a select group of patients with or without SLNB has been explored to compare the distant disease free, disease free and overall survival and axillary relapse rate (ARR).