Extensive Ductal Carcinoma In Situ Research Articles

Sneaky DCIS-looking Invasive Ductal Carcinoma of the Breast in the Extensive DCIS Background

Abstract Introduction/Objective In the most cases, invasive ductal carcinoma (IDC) of the breast is identifiable when they present with classic infiltrative growth pattern. However, subset of IDC can occur in a very sneaky way, significantly mimicking the appearance of ductal carcinoma in situ (DCIS). In this condition, it’s much more easier to miss the invasive component without pulling ancillary staining when morphologic findings are extremely compatible with DCIS, especially the diagnosis of DCIS was made on the previous biopsy. Methods/Case Report Retrospective analysis of the histologic and immunohistochemical findings of pure DCIS and DCIS-looking invasive ductal carcinoma. Results (if a Case Study enter NA) Here, we reported a 55 year-old female who was noted to have microcalcification at the 11:00 o’clock of the right posterior breast on routine mammographic examination in 09/2023. Biopsy of the calcification area in 10/2023 reported high grade DCIS (ER+ PR-). Histologic examination of subsequent mastectomy specimen showed two separate DCIS-looking areas. Immunohistochemical (IHC) staining showed that myoepithelial markers, p63 and smooth muscle myosin heavy chain (SMMHC), were retained at the periphery of all the expanded acini in one area. Unexpectedly and surprisingly, p63 and SMMHC were completely lost at the periphery of part of the DCIS-looking acini in another area, immunohistochemically compatible with the diagnosis of invasive ductal carcinoma admixed with DCIS. Conclusion Knowing that invasive ductal carcinoma of the breast can present as DCIS-looking morphology, especially given the condition that the diagnosis of DCIS was rendered on the previous biopsy, will enhance awareness of pathologists to recognize sneaky DCIS-looking invasive ductal carcinoma in the extensive DCIS background. In turn, this will prevent misdiagnosis and under-treatment of patients with invasive ductal carcinoma of the breast.

Pedicled Descending Branch Latissimus Dorsi Mini-Flap For Breast Reconstruction: Shoulder Functional and Aesthetic Outcomes

Abstract Background The cosmetic drawbacks of BCT are asymmetry, nipple or skin retraction, and volume loss which results in an unsatisfactory cosmetic outcome. Therefore, many volume replacement techniques were invented to counteract this. The commonest volume replacement technique for breast reconstruction is autologous LD flap in which skin paddle and subcutaneous tissue are harvested with the flap resulting in increased donor site morbidity. Objective To evaluate the latissimus dorsi mini-flap (LDMF) regarding the cosmetic outcomes and patient satisfaction. Moreover, it will evaluate procedure related complications and the benefit of using this procedure as a volume replacement to large breast defect after wide local excision in different breast quadrants excluding the lower inner quadrant (LIQ). Patients and Methods Our study was conducted on 15 patients to evaluate post-operative complications and patient satisfaction primarily. The results have demonstrated the safety of this procedure which is associated with a low rate of complications. Our study was designed to assess breast-sparing approaches using LD mini flap (LDMF) for reconstruction of the breast after wide local excision of large breast tumors that would result in otherwise unacceptable deformity. Results The LDMF generally is not a time-consuming technique as the average operative time was generally less than three hours. This time included the time for resection and the time waiting for frozen section results. The LDMF reconstruction was associated with considerable sensory preservation. This technique not only preserves most of the breast tissue but also, it spares us doing additional procedures such as nipple reconstruction. Avoidance the use of an implant is an additional advantage to the LDMF as this decrease the rate of infection and decrease the cost of the procedure. Conclusion LDMF volume replacement extends the role of breast-conserving surgery to a group of patients who are traditionally offered mastectomy. Despite the increasing use of Neoadjuvant chemotherapy, some patients have a disease that fails to respond or extensive DCIS and can, therefore, benefit from this oncoplastic technique. Frozen-section analysis of the tumor cavity is essential for surgical decision making. Our study had demonstrated the safety of this procedure which is associated with a low rate of complications. This technique has a high patient satisfaction rate wit agreeable cosmetic outcome. This technique can be used as a volume replacement to large breast defect in different breast quadrant except in lower inner quadrant which was not included in this study.

Abstract PO5-11-01: Audit of multidisciplinary team meetings for improving breast cancer care

Abstract Introduction: Multidisciplinary team (MDT) meeting is a well-established method of optimising care for breast cancer patients. However, its effectiveness has not been proven yet. The present study aims to audit the functioning of MDT at a tertiary care hospital in a low-middle income country. Methods: This study examines the prospectively maintained database of patients being discussed in MDT meetings occurring from August 2018 till June 2023. The MDT was suspended for few months in between owing to the COVID pandemic. The analysis was done in terms of indications of discussion, referring department, modification in the pre-MDT plan, new investigation advised, radiological and pathological concordance, significant change in management strategy and interesting cases. The analysis is both qualitative and quantitative. Quantitative analysis involves percentages, mean and median. Results: MDT at our institute was conducted every Saturday at 12 noon as an in-person meeting. The MDT was suspended from May 2020 till June 2021 in view of the pandemic. It was restarted in July 2021, on an online platform and is continued as such. A total of 473 cases were discussed with 181 (38.2%) benign causes and rest were malignant. The most common indication of discussion for malignant cases was feasibility of breast conservation (59.9%) followed by ruling out recurrence/residual disease (17.4%). The indication for benign cases was rad-path concordance and ruling out phyllodes in a case of fibroepithelial lesion. In 31.4% of the cases the plan was modified from the pre-MDT plan and there was improved care. 34.7% cases were advised to get a new investigation done in form of contrast enhanced mammogram or MRI. Seventy nine percent cases were feasible for BCS, and it was done involving few complex surgeries as well. The most common indication for deferring BCS was extensive DCIS. The total number of man hours spent in preparation as well as MDT were analysed with improved clinical care and revealed the MDT to be a time intensive exercise with poor efficacy in terms of hours spent per patient. The time to decision making was increased at an average of 7.5 days for these patients. Conclusion: MDT helps to achieve goals of superior clinical care for both benign and malignant breast disorders at the cost of increased time to decision. It is labour intensive with capability of changing decision in one third of the cases. However, MDT needs regular audit to ensure optimum care with available resources. Citation Format: Kanika Sharma, Gopal Puri. Audit of multidisciplinary team meetings for improving breast cancer care [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-11-01.

Current practice and provision of oncoplastic breast-conserving surgery in the UK: results of the ANTHEM national practice questionnaire.

Oncoplastic breast-conserving surgery (OPBCS) may be a better option than mastectomy ± immediate breast reconstruction (IBR) for women with breast cancer but studies directly comparing the techniques are lacking. We surveyed UK breast units to determine the current practice of OPBCS to inform the design of a future comparative study. An electronic survey was developed to explore the current practice of OPBCS. This included the local availability of volume displacement and/or replacement techniques; number of cases performed; contraindications and approach to contralateral symmetrisation. Summary data for each survey item were calculated and overall provision of care examined. 58 UK centres completed the survey, including 43 (74%) stand-alone breast and 15 (26%) combined breast/plastics units. Over 40% of units (n = 24) treated more than 500 cancers/year. Most units offered volume displacement techniques (TMs) (97%). Over two-thirds (n = 39. 67%) of units offered local perforator flaps (LPF). Approximately a half of units (10/19) not performing LPF were planning to introduce them in the next 12-24months. A third (n = 19, 33%) of units routinely performed simultaneous contralateral symmetrisation mostly with two-surgeon operating. There were limited oncological restrictions to OPBCS with no contraindications for multifocal cancers in most centres; 65% of units (36/55) offered OPBCS for multicentric disease. Extensive DCIS was a contraindication in a minority of units. OPBCS is widely available in the UK but contraindications and approaches to contralateral symmetrisation were variable. Work is now needed to prospectively evaluate the outcomes of OPBCS vs mastectomy ± IBR to support informed decision-making.

Abstract P3-05-27: The impact of co-existing ductal carcinoma in situ in invasive early hormone receptor positive breast cancer on the genomic and clinical risk of recurrence

Abstract Background: Invasive early breast cancer (IBC) often presents with a co-existing ductal carcinoma in situ (DCIS) component, while about 5% of the cases present with an extensive (>25%) intraductal component (EIC). The presence of a DCIS component was previously shown to be associated with favorable clinico-pathological characteristics and survival outcomes. However, the association between co-existing DCIS and genomic risk of recurrence is unclear. Methods: Patients with early hormone receptor positive (HR+) HER2neu-negative (HER2-) breast cancer and known OncotypeDX breast recurrence score (RS), who underwent breast surgery in our institute, were included. A natural language processing (NLP) algorithm was used to identify co-existence of extensive DCIS (DCIS-H) and non-extensive DCIS (DCIS-L) in surgical pathological reports. Genomic risk was determined using OncotypeDX RS, while clinical risk was calculated according to the MINDACT criteria, based on tumor size and grade. The genomic and clinical risks of DCIS-H, DCIS-L and pure IBC (No-DCIS) were compared. Results: A total of 45 (5%) DCIS-H cases, 468 (56%) DCIS-L cases and 328 (39%) No-DCIS cases were identified. DCIS-H cases presented with less aggressive clinico-pathological characteristics, such as lower proportions of histologic grade III (10% vs 26% vs 21%) and lower proportions of node-positive disease (13% vs 18% vs 21%), compared to DCIS-L and No-DCIS cases, respectively. The distribution of OncotypeDX RS significantly varied between the groups. DCIS-H tumors were less likely to have a high RS and more likely to have a low or intermediate RS compared to DCIS-L and No-DCIS tumors (High RS: 4% vs 20% vs 20%, Low + intermediate RS: 96% vs 80% vs 80%, respectively; p=0.04). Additionally, the proportions of high clinical risk cases were lower in the DCIS-H group compared to the DCIS-L and No-DCIS groups (42% vs 53% vs 50%, respectively; p=0.002). Based on genomic and clinical risk and current guidelines, we found that women presented with an extensive DCIS component (DCIS-H) had a lower probability of receiving an adjuvant chemotherapy recommendation compared to women presented with a non-extensive DCIS component (DCIS-L) or pure IBC (No-DCIS) (11% vs 29% vs 25%, respectively; p=.035). No differences in disease recurrence were detected between the groups. Conclusions: Co-existing extensive DCIS in invasive early HR+Her2- breast cancer is significantly correlated with lower genomic and clinical risk of recurrence and a smaller chance for chemotherapy recommendation. The rarity of this condition (5% of cases) limited our ability to detect differences in outcomes. These findings warrant future studies of the underlying genomic landscape of co-existing extensive DCIS. Citation Format: Yael Bar, Kfir Bar, Judith Ben- Dror, Didi Feldman, Meishar Shahoha, Ahuva Weiss-Meilik, Nachum Dershowitz, Wolf Ido, Amir Sonnenblick. The impact of co-existing ductal carcinoma in situ in invasive early hormone receptor positive breast cancer on the genomic and clinical risk of recurrence [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 P3-05-27.

Pathologic Response of Associated Ductal Carcinoma In Situ to Neoadjuvant Systemic Therapy: A Systematic Review

Contrary to traditional assumptions, recent evidence suggests that neoadjuvant systemic therapy (NST) given for invasive breast cancer may eradicate co-existent ductal carcinoma in-situ (DCIS), which may facilitate de-escalation of breast resections. The aim of this systematic review was to assess the eradication rate of DCIS by NST given for invasive breast cancer. Searches were performed in MEDLINE using appropriate search terms. Six studies (N = 659) in which pathological data were available regarding the presence of DCIS prior to neoadjuvant chemotherapy (NACT) were identified. Only one study investigating the impact of neoadjuvant endocrine therapy (NET) met the search criteria. After pooled analysis, post-NACT pathology showed no residual DCIS in 40.5% of patients (267/659; 95% CI: 36.8-44.3). There was no significant difference in DCIS eradication rate between triple negative breast cancer (TNBC) and HER2-positive disease (45% vs. 46% respectively). NET achieved eradication of DCIS in 15% of patients (9/59). Importantly, residual widespread micro-calcifications after NST did not necessarily indicate residual disease. In view of the results of the pooled analysis, the presence of extensive DCIS prior to NST should not mandate mastectomy and de-escalation to breast conserving surgery (BCS) should be considered in patients identified by contrast enhanced magnetic resonance imaging (CE-MRI).

Oncological Safety of Skin-Sparing Mastectomy and Immediate Breast Reconstruction in Extensive Ductal Carcinoma In Situ

IntroductionSkin-sparing mastectomy (SSM) with immediate breast reconstruction is the ideal treatment for interested and suitable patients with extensive ductal carcinoma in situ (DCIS). There is no guideline to indicate on how large DCIS the procedure can be performed safely. The primary target of this study was to define the oncological safety of SSM in extensive pure DCIS. The secondary target was to find predictive factors for DCIS upstaging to invasive disease. Materials and methodsA total of 71 consecutive patients with extensive pure DCIS and undergoing SSM with immediate latissimus dorsi (LD) breast reconstruction were retrospectively evaluated. ResultsThe median size of DCIS lesion in preoperative imaging was 60 mm, the median weight of mastectomy specimen was 350 g, and the median resection margin (RM) was 2.0 mm. A total of 20 patients (28%) had an RM less than 0.5 mm and nine patients (13%) had ink positive margins. Six patients having positive RM underwent reoperation. A total of 29 patients (41%) presented invasive cancer foci in final histopathological assessment and nine patients (13%) had an axillary metastasis. Adjuvant therapy was given to 23 patients presenting invasive cancer. There were no local recurrences or distant metastases (0%, 95% confidence interval 0-0.051) during the mean follow-up of 71 mo. None of the factors evaluated predicted upstaging to invasive disease. ConclusionsSSM with immediate breast reconstruction in patients with extensive DCIS is oncologically safe even when the margins are close or positive. Additional invasive foci and solitary axillary lymph node metastases are frequent but do not worsen the outcome.

Abstract P3-19-19: Intraoperative Radiation Therapy (IORT) : A large integrated healthcare system’s approach and outcomes

Abstract Background: With TARGIT-R(Retrospective) showing a higher-than-expected ipsilateral breast tumor recurrence (IBTR) the community setting for intraoperative radiation therapy (IORT), we evaluated IORT outcomes in an integrated health care system.Methods: A retrospective review of early breast cancer patients who received IORT between February 2014-February 2020 was performed. IORT was offered at a single medical center within a large integrated healthcare system. Criteria for IORT included patients ≥50 years with T1, low to intermediate grade, endocrine-responsive HER2- invasive ductal carcinoma. All breast cancer patients were reviewed at weekly multidisciplinary breast conferences, and IORT was offered when patients met the eligibility criteria. Primary outcomes include IBTR, mortality, and complications. Results: Of 5,731 potentially eligible patients, 245 patients (4.3%) underwent IORT. Mean age was 65.4 ± 0.4 years with median follow-up 3.5 years ± 2.2 months. Based on American Society of Radiation Oncology guideline, 51% were suitable, 38.4% cautionary, and 10.6% unsuitable candidates based on the final pathology. The patients were reassigned to the cautionary group because of the margin width and/or extensive DCIS. Unintended boost (primary IORT followed by whole-breast radiation) was given in 6.5% of IORT patients. At median follow-up of 3.5 years, IBRT was 3.7% for all patients. There was one breast-cancer-related mortality (0.4%), and 7 mortality (2.9%) from other causes. Although not statistically significant, there was a trend towards higher recurrence in those not adherent with endocrine treatment than those who were (7.4% vs 1.9%, p=0.07). The overall complication rate was 14.7% with seroma as the most common.Conclusions: At 3.5-year follow-up, our IORT IBTR rate of 3.7%. Our protocol subsequently was modified to require all IORT patients to receive surgical shave margins, WBI for all cautionary patients on the final pathology, and requirement of endocrine treatment. Citation Format: Annie Tang, Jason Kelly, Elizabeth Cureton, Jonathan Svahn, Eva Thomas, Liisa Lyon, Veronica Shim. Intraoperative Radiation Therapy (IORT) : A large integrated healthcare system’s approach and outcomes [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-19.

From modified radical mastectomy to infra-radical mastectomy: a phase I study for surgical de-escalation focusing on pathological analyses.

Despite that breast conservative therapy became the standard of care in breast cancer, modified radical mastectomy, a large mutilating surgery, is still required for an important number of patients. In order to improve the quality of life and the psychological aspects of a surgery involving the femininity of woman, we developed a new less invasive procedure called infra-radical mastectomy. It aims to save the neckline of patients by the maintenance of the peripheral skin-fatty flap that constitutes the base for implantation of the breast. This phase I study analyzed the feasibility of this procedure using outcome of anatomo-pathological analyses as primary endpoint. Between March 2015 and July 2017, all women with operable breast cancer without signs of lymph node invasion were invited to participate in the study in the 2 participating institutions. After a water-assisted dissection of the peri-glandular space, an enucleation of the breast was performed by a cold knife which represents the infra-radical mastectomy. A peri-glandular re-excision (PGR) of the skin and the fat tissue surrounding the gland was then achieved to obtain an MRM. This PGR underwent a careful pathological examination (10 samples per patient). Moreover, the tissue volume and the skin surface of the PGR were quantified. A total of 53 patients (median age: 60 years) were prospectively recruited. The pathological analysis of peri-glandular biopsies revealed none residual invasive carcinoma, 1% of biopsies contained focal ductal carcinoma in situ (DCIS) and 0.4% atypical hyperplasia corresponding to 4 and 2 patients respectively. These 4 patients with residual DCIS were preoperatively diagnosed with extensive DCIS. On average after an infra-radical mastectomy, 37% of the volume and 53% of the skin surface of a complete modified radical mastectomy were sparred. The evaluation of biopsies from peri-glandular tissue suggests that infra-radical mastectomy should be further evaluated except for patients diagnosed with extensive DCIS which must be excluded of this infra-radical approach. Additional work is needed to evaluate cosmetic outcome and impact on quality of life, the need of radiotherapy and the oncological long-term outcome.

Estrogen receptor expression in normal breast epithelium in invasive ductal carcinoma

Objectives: Invasive ductal carcinomas (IDCs) are the most important group of malignant breast tumors and constitute 75-80% of breast carcinomas. While IDCs often present with ductal carcinoma in situ (DCIS), they sometimes include a low level of DCIS or they do not include any accompanying DCIS at all. We planned this study to compare estrogen receptor (ER) expression levels in normal mammary epithelium in IDCs with extensive DCIS (Group I) and IDCs without DCIS (Group II). Methods: Eighty IDC cases selected from among samples that were analyzed in our pathology laboratory. The cases were assessed retrospectively in light of immunohistochemical analysis results and pathology reports. Evaluation of immunohistochemistry: ER positivity in IDC was defined with a nuclear staining of more than 10% of cancer cells regardless of intensity of staining. Presence of cells showing nuclear staining for normal breast epithelium was classified in 4 groups according to their quantity and intensity. These were: 0-None: No staining was observed, 1-Single: One or two positive cells, 2-Dispersed: Dispersed positive cells surrounded by negative cells, 3-Adjoined: 10 or more positive cells contacting each other. Results: Statistically no significant difference was found between Group I and Group II in terms of ER expression. Group I were more prevalent in younger and in the premenopausal period than Group II. Conclusions: According to our study, there was no difference between Group I and Group II in terms of ER expression. But the significantly presence Group I in more young people and in premenopausal women suggests that these carcinomas develop due to high estrogen levels and that Group II develop independently than estrogen. This suggests that these groups may have different carcinogenesis and etiologies. We therefore think that this first study on IDCs with extensive DCIS and IDCs without DCIS should be supported by new research studies.

Postmastectomy radiation therapy in early breast cancer: Utility or futility?

Postmastectomy radiation therapy (PMRT) has been shown to reduce the risk of locoregional recurrence (LRR), in patients with locally advanced breast cancer who are considered of high-risk because of large tumors (>5 cm) or presence of axillary lymph-node involvement, as well as to reduce breast cancer mortality. However, controversy still remains with respect to indication of PMRT in case of early-stages invasive tumors. This review aims to analyze the impact that PMRT has on final results in women with breast tumors in different scenarios that would otherwise be considered as early breast cancer, such as extensive DCIS, tumors without axillary lymph-node involvement or with minimal microscopic nodal-involvement. The existence of risk factors including young age, premenopausal status, and presence of lymphovascular invasion (LVI), high grade or tumor size >2 cm has been associated with an increased risk of LRR in these patients at early-stages and advises to consider PMRT in selected cases.

A Nomogram to Predict Factors Associated with Lymph Node Metastasis in Ductal Carcinoma In Situ with Microinvasion.

Ductal carcinoma in situ (DCIS) with foci of invasion measuring ≤ 1mm (DCISM), represents < 1% of all invasive breast cancers. Sentinel lymph node biopsy (SLNB) has been a standard component of surgery for patients with invasive carcinoma or extensive DCIS. We hypothesize that selective performance of SLNB may be appropriate given the low incidence of sentinel node (SN) metastasis for DCISM. We investigated the clinicopathologic predictors for SN positivity in DCISM, to identify which patients might benefit from SLNB. A retrospective review of the National Cancer Database was performed for cases from 2012 to 2015. Clinical and tumor characteristics, including SN results, were evaluated, and Pearson's Chi square tests and logistic regression were performed. Of 7803 patients with DCISM, 306 (4%) had at least one positive SN. Patients with positive SNs were younger, more often of Black race, had higher-grade histology and larger tumor size, and were more likely to have lymphovascular invasion (LVI; all p < 0.001). In an adjusted model, the presence of LVI was associated with the highest odds ratio (OR) for node positivity (OR 8.80, 95% confidence interval 4.56-16.96). Among women with DCISM, only 4% had a positive SN. Node positivity was associated with more extensive and higher-grade DCIS, and the presence of LVI was strongly correlated with node positivity. Our data suggest that LVI is the most important factor in determining which patients with DCISM will benefit from SN biopsy.

Oncoplastic Central Partial Mastectomy and Neoareolar Reduction Mammoplasty with Immediate Nipple Reconstruction: An Initial Report of a Novel Option for Breast Conservation in Patients with Subareolar Tumors.

Breast-conserving therapy (BCT) has been associated with better quality of life and cosmetic outcomes than mastectomy. However, subareolar cancers abutting the nipple-areolar complex (NAC) present a unique cosmetic and oncologic challenge. Oncoplastic central partial mastectomy and neoareolar reduction mammoplasty with immediate nipple reconstruction is a novel technique that can permit BCT for these patients. This study enrolled consecutive patients with central tumors during 2017-2018 who underwent central partial mastectomy reconstructed with neoareolar reduction mammoplasty and immediate nipple reconstruction. Patient demographics, imaging and pathology size, margin width, mastectomy and reexcision rates, and cosmesis were evaluated. The study identified 23 sequential patients. The average patient age was 60.5 ± 12.3years, and the average body mass index was 29.4 ± 5.7kg/m2. The mean lesion size was 51.5 ± 43.0mm on preoperative imaging, and the average disease span shown by the final pathology was 59.5 ± 45.3mm. "No ink on tumor" was achieved for 22 patients (95.7%). In 13 patients (56.5%), the margins were inadequate for ductal carcinoma in situ (DCIS) (n = 12) or invasive cancer (n = 1). Good to excellent cosmetic results were achieved for 21 patients (95.5%). Complications occurred for six patients (26.1%), including three patients with ischemia of the reconstructed NAC. The single-stage operation described in this report can allow patients with cancers abutting the NAC to consider BCT. This technique allows patients to avoid mastectomy and to minimize the number of operations required for reconstruction while maximizing cosmetic outcomes. In the study cohort, the presence of extensive DCIS resulted in a significant need for reexcision, which could be performed successfully without compromise to cosmetic outcome.

Comparative analysis of margin status in breast conservation surgery and its correlation with subsequent re-excision findings.

SummaryPurposeBreast-conservation surgery (BCS) has become a standard treatment option for invasive breast carcinoma (IBC) and ductal carcinoma in situ (DCIS). The strongest predictor of local recurrence remains the surgical margin status. We evaluated the margin positivity by quantifying the tumor on positive margins and analyzing the histologic factors including type and extent in determining the likelihood of residual disease upon re-excision.MethodRetrospective analysis of 210 BCS performed at Mount Sinai Medical Center from the period of January 2011 - December 2017 revealed that 58 had IBC, DCIS, or both, with positive margins that were followed by re-excision.ResultThe margins had IBC in 18 (31%), DCIS in 32 (55.2%) and both in 8 (13%) cases. Thirty-eight cases (65.5%) were free of carcinoma on re-excision. Of 40 cases with margins positive for DCIS, 16 (40%) had residual DCIS. Of 26 cases with IBC at the margins, and 5 had residual disease (19%). This difference was statistically significant (p = 0.002). Of 21 cases with extensive DCIS, 12 had residual disease (p = 0.02) as compared to only 4 out of 19 without extensive DCIS. None of the cases with clinging/micro-papillary DCIS had residual disease, while 51% of the other types (solid, cribriform, come-do) had residual disease (p = 0.02). The area of DCIS as measured on the involved margin correlated with the amount of residual disease on re-excision (p = 0.03).ConclusionMargins positive for DCIS are more likely to have residual disease on re-excision in comparison to margins positive for only IBC. The type and extent of DCIS appears to influence the likelihood of residual disease.

Extreme Oncoplastic Surgery for Multifocal/Multicentric and Locally Advanced Breast Cancer.

Introduction Breast conserving surgery (BCS) followed by radiation therapy (RT) has become the preferred alternative to mastectomy for patients with early stage breast cancer (BC). Randomized trials have confirmed equivalent locoregional control and overall survival for BCS and mastectomy. Extreme Oncoplasty (EO) extends the indications of BCS for patients who would otherwise require mastectomy, ensuring better aesthetic outcomes and oncological safety. Methods BC patients with multifocal/multicentric (MF/MC) tumors, extensive DCIS, or large tumor >50mm underwent EO at our breast unit. Therapeutic reduction mammaplasty (TRM) with wise pattern preoperative markings and dual pedicle technique involving parenchymal rearrangement was used for oncoplastic reconstructions in majority of the cases followed by RT. Patient reported outcome measures (PROMs) were assessed using the validated Breast-Q questionnaire. Results Of the 39 patients in the study, 36 had unilateral and 3 had bilateral BC. Mean age was 47.2 years. Median tumor size was 75mm. 17 (43.6%) patients received NACT; none achieved a complete clinical response. 28 (71.8%) patients were administered to adjuvant chemotherapy. 33(84.6%) patients received RT to the breast with a median dose of 50Gy in 28 fractions and a boost dose of 10Gy in 5 fractions to the tumor bed. No major complications or local recurrences were observed. Excellent Breast-Q scores were observed in patients undergoing EO after 12 months of follow-up. Conclusion EO followed by RT results in acceptable local-regional control, low rate of complications, and high patient satisfaction. In selected patients, EO could provide a safe alternative for breast conservation surgery instead of mastectomy.

Abstract P3-07-06: Evidence for tumor heterogeneity and clonal evolution during invasive progression in breast cancer

Abstract Purpose: Intratumoral heterogeneity is well recognized to be an important driver of treatment resistance and metastasis. We undertook this N of three study to measure the degree of heterogeneity in three large preinvasive lesions, all with invasive components to determine the relationship between tumor heterogeneity, spatial distribution, clonal evolution, and invasive progression. Methods: We identified patients A, B, C with extensive DCIS measuring 7.5 cm, 6 cm, and 7 cm associated with 0.3 cm, 3.8cm, and 3.4 cm of an invasive component and 0, 7 and 1 positive lymph node, respectively. We sequenced the tumor sample for Case A from 32 unique blocks with precise geospatial localization; invasive cancer was identified in 3 of 32 blocks. Case B had 26 blocks sequenced with invasive cancer in 13 of 26 blocks. Case C had 23 blocks sequenced with invasive in 11 of 23 blocks. For germline reference, we sequenced DNA from an uninvolved tissue from each case. NGS libraries were made from FFPE derived DNA (20-40ng) for full exome sequencing. Variant calling was performed by GATK HaplotypeCaller, Platypus and Mutect. Identified somatic mutations were annotated with Oncotator and pathway enrichment analysis was performed with Bioconductor. To investigate the clonal evolution and progression history, phylogenetic trees were constructed in R and sub-clonal analysis was performed with Treeomics. Results: The sequence data was analyzed with Platypus, MuTect and GATK HaplotypeCaller. The somatic mutation sites were concatenated into one sequence for each sample. Both neighbor-joining trees and maximum parsimony trees were built for each case. Phylogenetic analysis and sub-clonal analysis support the multi-clonal invasion model of invasive cells, in which invasive cancer can evolve from multiple clades, either early or late in the evolutionary history, independently. Dense sampling allowed reconstruction of the temporal order of mutations that accumulated in the cell lineage of the invasive cancers. Furthermore, phylogeny and sub-clone spatial analysis revealed that distant regions may be closely genetically related and showed a weak spatial sub-clone clustering pattern, which is consistent with the predictions of Big Bang model. For driver genes, we find that except for SETD2 in Case B, the majority of driver gene mutations are sub-clonal. Somatic mutations on ATP-binding cassette (ABC) transporter pathway was found in all cases. Conclusions: Extensive sampling and sequencing of tumors yields important insights about tumor heterogeneity and tumor progression of DCIS to invasive cancer. Variable invasive propensity was identified, with foci of invasion were geospatially associated with preinvasive regions of progressively higher mutational load. Citation Format: Ding Y, Marks J, King L, Hardman T, Hall A, Mallo D, Rodrigo A, Maley C, Hwang S. Evidence for tumor heterogeneity and clonal evolution during invasive progression in breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-07-06.

Local Relapse After Breast-Conserving Therapy Versus Mastectomy for Extensive Pure Ductal Carcinoma In Situ ≥4 cm

The optimal treatment for patients with extensive pure ductal carcinoma in situ (DCIS) ≥4cm is controversial. This study evaluates local relapse according to type of local therapy: mastectomy, breast-conserving surgery (BCS) alone, and BCS+radiation therapy (RT). Subjects were female patients who received diagnoses of pure DCIS ≥4cm between 1989 and 2010 and were referred to British Columbia Cancer. Clinicopathologic and treatment characteristics were compared between treatment cohorts. Local relapse (LR) was estimated using competing risk analysis. Multivariable analysis was performed using Cox regression analysis. Patients had the following treatments: 490 mastectomy, 38 BCS alone, and 192 BCS+RT. The 10-year cumulative incidence of LR was 16% after BCS (95% confidence interval [CI], 6-29%), 8% after BCS+RT (95% CI, 4-12%), and 2% after mastectomy (95% CI, 1-4%). On multivariable analysis, estrogen receptor-negative disease (hazard ratio [HR], 3.32; 95% CI, 1.08-10.18; P=.04) and positive margins (HR, 3.55; 95% CI, 1.56-8.05; P=.002) were associated with increased LR. BCS alone (HR, 7.87; 95% CI, 2.82-21.92; P<.0001), BCS+RT+no boost (HR, 3.80; 95% CI, 1.56-9.28; P=.003), and BCS+RT+boost (HR, 5.76; 95% CI, 2.59-12.83; P<.0001) were all associated with a higher risk of relapse relative to mastectomy. Mastectomy remains a standard local treatment option for extensive DCIS, but BCS+RT may also be reasonably considered in selected patients with a careful discussion of the benefits, side effects, and patient preferences.

Clinical presentation of ductal carcinoma in situ of breast with intraluminal crystalloids: Radiologic-histologic correlation

Intraluminal crystalloids have rarely been described in the breast, particularly in cases with ductal carcinoma in situ (DCIS). We recently encountered a case of DCIS of the breast associated with numerous intraluminal crystalloids. The patient presented with a mass in the right breast, and microcalcifications were detected on screening and diagnostic mammograms; the patient underwent needle biopsies, lumpectomy, and skin-sparing mastectomy. Invasive ductal carcinoma associated with extensive DCIS was diagnosed. Multiple refractile, eosinophilic crystalloids, with variable morphologies including rectangular, triangular and needle-like with sharp borders, were observed within the lumina of DCIS, besides calcium phosphate microcalcifications. We report this case together with a literature review on crystalloid-containing lesions in breast and non-breast tissues. We also studied radiologic findings of these crystalloids using a specimen radiograph.

Not All Ductal Carcinomas In Situ Are Created IDLE (Indolent Lesions of Epithelial Origin).

Mammographic screening has increased the incidence of ductal carcinoma in situ (DCIS), but this has not been accompanied by a decline in the incidence of invasive carcinoma (IC). Consequently, the surgical treatment of DCIS has recently been questioned, with some advocating only surveillance (with or without neoadjuvant endocrine therapy) after a core biopsy diagnosis of DCIS. To examine the predictive value of a core biopsy diagnosis of DCIS, particularly the upgrade rate to IC, and to identify associated factors. Using the pathology database, we identified 2943 cases of DCIS diagnosed on core biopsy from 2000 to 2015, of which 229 cases (8%) later had the stage upgraded to IC. Ages ranged from 25 to 90 years (mean, 59 years). The DCIS presented with calcifications in 151 of 229 cases (65.9%), was widespread in 26 of 151 cases (17%), had a mass or density present in 70 of 229 cases (31%), with heterogeneous echogenic features in 44 of those 70 cases (63%), and an enhancement upon magnetic resonance imaging in 8 of 229 cases (3.5%). Of the 229 cases, the DCIS grades were as follows: low in 29 cases (13%), intermediate in 79 cases (36%), and high in 121 cases (53%). Of the 229 cases, necrosis was present in 152 (66.4%) and was comedo necrosis in 99 cases (43%). Of the 229 cases of IC, the tumor stage was as follows: microIC in 36 (16%), T1a in 119 (52%), T1b in 35 (15%), T1c in 28 (12%), T2 in 8 (3%), and T3 in 3 cases (1%). Axillary lymph nodes were staged in 167 patients as follows: N0, 141 cases (84%); N0(i+), 14 cases (8%); and N1, 12 cases (7%). The 12 N1 cases were subclassified by T stage as follows: T1a, 1 case (8%); T1b, 4 cases (33%); T1c, 2 cases (17%); T2, 4 cases (33%); and T3, 1 case (8%). The IC cases of stage upgrading were predominantly smaller than 2 cm (218 of 229; 95%), and more than two-thirds were smaller than 0.5 cm (155 of 229; 95%), most of which were accompanied by extensive DCIS. Approximately one-half of the upgrades were associated with high-grade DCIS, especially with comedo necrosis; nevertheless, the other one-half of the upgrades were due to low- and intermediate-grade DCIS and should not be underestimated. There were few positive results from axillary lymph node biopsies, but they occurred in 3% (7 of 218) of the carcinomas smaller than 2 cm. Our findings indicate that caution is needed when DCIS cases diagnosed by core biopsy are treated nonsurgically with surveillance (with or without neoadjuvant endocrine therapy), given the number of cases (229 of 2943; 8%) that are upgraded to IC and those with axillary lymph node metastases (12 of 167; 7%).

135 Late Recurrence of Breast Carcinoma as Intraepidermal Paget Disease in the Drainage Sites: A Unique Case

The Paget disease of breast or extramammary localizations represents involvement of the epidermis by adenocarcinoma. In breast, usually the underlying dermis/subcutis harbors ductal carcinoma in situ (DCIS) or invasive carcinomas with intraductal component. The intraductal carcinoma is high grade with necrosis, practically in all cases. Immunohistochemically, most are Her2 positive and negative for hormonal receptors. Recurrence of breast carcinomas as Paget disease occurs especially after DCIS following conservative or total mastectomy with or without conservation of the nipple-areolar complex. The previous core biopsy track or surgical scars are rare sites of recurrent disease. A 72-year-old woman with a history of extensive DCIS treated with total mastectomy eight years ago developed skin erythematous lesions around two surgical drainage sites. An incisional biopsy revealed in both lesions large atypical cells within epidermis with a pagetoid pattern. The immunohistochemical reactions showed that the cells were positive for cytokeratin 7 and Her2, and negative for hormonal receptors, cytokeratin 5/6, p63, and Melan A. We present a unique case of recurrence of DCIS as intraepidermal Paget disease in drainage sites, eight years later of total mastectomy. This kind of recurrence is very exceptional, with only one case reported in a core biopsy track. It has not been previously described in drainage sites. It is necessary to consider the possibility of recurrence of breast cancer as Paget disease as a late event and only with epidermal involvement.