The African Research Group for Oncology: A decade fostering colorectal cancer research in Nigeria.

The African Research Group for Oncology (ARGO) was formed in 2013 to undertake methodologically rigorous cancer research in Nigeria, and to strengthen cancer research capacity in the country through training and mentorship of physicians, scientists, and other healthcare workers. Here, we describe how ARGO's work in colorectal cancer (CRC) has evolved over the past decade. This includes the consortium's scientific contributions to the understanding of CRC in Nigeria and globally and its research capacity-building program.

Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is lethal in 88% of patients1, yet harbours mutation-derived T cell neoantigens that are suitable for vaccines 2,3. Here in a phase I trial of adjuvant autogene cevumeran, an individualized neoantigen vaccine based on uridine mRNA-lipoplex nanoparticles, we synthesized mRNA neoantigen vaccines in real time from surgically resected PDAC tumours. After surgery, we sequentially administered atezolizumab (an anti-PD-L1 immunotherapy), autogene cevumeran (a maximum of 20 neoantigens per patient) and a modified version of a four-drug chemotherapy regimen (mFOLFIRINOX, comprising folinic acid, fluorouracil, irinotecan and oxaliplatin). The end points included vaccine-induced neoantigen-specific T cells by high-threshold assays, 18-month recurrence-free survival and oncologic feasibility. We treated 16 patients with atezolizumab and autogene cevumeran, then 15 patients with mFOLFIRINOX. Autogene cevumeran was administered within 3 days of benchmarked times, was tolerable and induced de novo high-magnitude neoantigen-specific T cells in 8 out of 16 patients, with half targeting more than one vaccine neoantigen. Using a new mathematical strategy to track T cell clones (CloneTrack) and functional assays, we found that vaccine-expanded T cells comprised up to 10% of all blood T cells, re-expanded with a vaccine booster and included long-lived polyfunctional neoantigen-specific effector CD8+ T cells. At 18-month median follow-up, patients with vaccine-expanded T cells (responders) had a longer median recurrence-free survival (not reached) compared with patients without vaccine-expanded T cells (non-responders; 13.4 months, P = 0.003). Differences in the immune fitness of the patients did not confound this correlation, as responders and non-responders mounted equivalent immunity to a concurrent unrelated mRNA vaccine against SARS-CoV-2. Thus, adjuvant atezolizumab, autogene cevumeran and mFOLFIRINOX induces substantial T cell activity that may correlate with delayed PDAC recurrence.

Risk of Contralateral Breast Cancer in Women with Ductal Carcinoma In Situ Associated with Synchronous Ipsilateral Lobular Carcinoma In Situ.

BACKGROUND: Lobular carcinoma in situ (LCIS) is a risk factor for breast cancer, but the effect of LCIS found in association with ductal carcinoma in situ (DCIS) is unknown. In this study, we compared contralateral breast cancer (CBC) and ipsilateral breast tumor recurrence (IBTR) rates among women with DCIS with or without synchronous ipsilateral LCIS treated with breast-conserving surgery (BCS). METHODS: DCIS patients undergoing BCS from 2000 to 2011 with a contralateral breast at risk were stratified by the presence or absence of synchronous ipsilateral LCIS with the index DCIS (DCIS + LCIS vs. DCIS). Those with contralateral, bilateral, or prior ipsilateral LCIS were excluded. Associations of patient, tumor, and treatment factors with CBC and IBTR were evaluated. RESULTS: Of 1888 patients identified, 1475 (78%) had DCIS and 413 (22%) had DCIS + LCIS. At median follow-up of 7.2 (range 0-17) years, 307 patients had a subsequent first breast event; 207 IBTR and 100 CBC. The 10-year cumulative incidence of IBTR was similar in both groups: 15.0% vs. 14.2% (log-rank, p = 0.8) for DCIS + LCIS vs. DCIS, respectively. The 10-year cumulative incidence of CBC was greater in the DCIS + LCIS group: 10.9% vs. 6.1% for DCIS (log-rank, p < 0.001). After adjustment for other factors, CBC risk remained higher in DCIS + LCIS compared with DCIS (hazard ratio 2.06, 95% confidence interval 1.36-3.11, p = 0.001); there was no significant difference in IBTR risk. CONCLUSIONS: Compared with DCIS alone, DCIS + LCIS is associated with similar IBTR risk but double the risk of CBC. This finding should inform treatment decisions, in particular regarding endocrine therapy for risk reduction.

Delay in radiotherapy is associated with an increased risk of disease recurrence in women with ductal carcinoma in situ.

BACKGROUND: The current study was conducted to examine the association between ipsilateral breast tumor recurrence (IBTR) and the timing of radiotherapy (RT) in women with ductal carcinoma in situ (DCIS) undergoing breast-conserving surgery (BCS). METHODS: Women with DCIS who were treated with BCS and RT from 1980 through 2010 were identified from a prospectively maintained database. IBTR rates, measured from the time of RT completion, were compared between those who initiated RT ≤8 weeks, >8 to 12 weeks, and >12 weeks after the completion of surgery. The association between RT timing and IBTR was evaluated by Kaplan-Meier and log-rank analyses; Cox modeling was used for multivariable analysis. RESULTS: A total of 1323 women met the inclusion criteria. The median follow-up was 6.6 years, with 311 patients followed for ≥10 years. A total of 126 IBTR events occurred. Patients were categorized by RT timing: 806 patients (61%) with timing of ≤8 weeks, 386 patients (29%) with timing of >8 to 12 weeks, and 131 patients (10%) with timing >12 weeks. The 5-year and 10-year IBTR rates were 5.8% and 13.0%, respectively, for RT starting ≤8 weeks after surgery; 3.8% and 7.6%, respectively, for RT starting >8 to 12 weeks after surgery; and 8.8% and 23.0%, respectively, for an RT delay >12 weeks after surgery (P = .004). On multivariable analysis, menopause (hazard ratio [HR], 0.54; P = .0009) and endocrine therapy (HR, 0.45; P = .002) were found to be protective against IBTR, whereas a delay in RT >12 weeks compared with ≤8 weeks was associated with a higher risk of IBTR (HR, 1.92; P = .014). There was no difference in IBTR noted between RT initiation at ≤8 weeks and initiation at >8 to 12 weeks after BCS (P = .3). CONCLUSIONS: A delay in RT >12 weeks is associated with a significantly higher risk of IBTR in women undergoing BCS for DCIS. Efforts should be made to avoid delays in starting RT to minimize the risk of disease recurrence. Cancer 2018;124:46-54. © 2017 American Cancer Society.

Contralateral Breast Cancer Risk in Women with Ductal Carcinoma In Situ: Is it High Enough to Justify Bilateral Mastectomy?

BACKGROUND: Women with ductal carcinoma in situ (DCIS) are increasingly choosing bilateral mastectomy. We sought to quantify rates of contralateral breast cancer (CBC) and ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) for DCIS, and to compare risk factors for CBC and IBTR. METHODS: From 1978 to 2011, DCIS patients undergoing BCS with a contralateral breast at risk were identified from a prospectively maintained database. The association of clinicopathologic and treatment factors with CBC and IBTR were evaluated using Kaplan-Meier analysis, multivariable Cox regression, and competing risk regression (CRR). RESULTS: Of 2759 patients identified, 151 developed CBC and 344 developed IBTR. Five- and 10-year Kaplan-Meier CBC rates were 3.2 and 6.4%. Overall, 10-year IBTR rates were 2.5-fold higher than CBC rates, and, without radiation, 4-fold higher. On CRR, 5- and 10-year rates were 2.9 and 5.8% for CBC, and 7.8 and 14.5% for IBTR. CBC risk and invasive CBC risk were not significantly associated with age, family history, presentation, nuclear grade, year of surgery, or radiation. By multivariable Cox regression, endocrine therapy was associated with lower CBC risk (hazard ratio 0.57, p = 0.03). Ten-year risk of subsequent CBC in the subset of patients who developed IBTR was similar to the cohort as a whole (8.1 vs. 6.4%). CONCLUSIONS: CBC rates were low across all groups, including those who experienced IBTR. CBC was not associated with factors that increase IBTR risk. While factors associated with IBTR risk are important in decision making regarding management of the index DCIS, they are not an indication for contralateral prophylactic mastectomy.

Outcomes for Women with Minimal-Volume Ductal Carcinoma In Situ Completely Excised at Core Biopsy.

BACKGROUND: Overdiagnosis and overtreatment of ductal carcinoma in situ (DCIS) are concerns, especially for women with low-volume, screen-detected DCIS. This study aimed to evaluate the outcomes for such patients. METHODS: Women who had minimal-volume DCIS (mDCIS, defined as DCIS diagnosed by core biopsy but with no residual disease on the surgical excision) treated with breast-conserving surgery from 1990 to 2011 were identified. Ipsilateral and contralateral breast events (IBE and CBE) were compared by competing-risk (CR) analysis. Kaplan-Meier (KM) estimates and log-rank tests were used to evaluate covariates. RESULTS: The study identified 290 cases of mDCIS. The median age of the patients was 53 years. Radiation therapy (RT) was performed for 27.6% and endocrine therapy for 16.2% of the patients. The median follow-up period was 6.8 years. Overall, the IBE rates were 4.3% at 5 years and 12.3% at 10 years. Among the women not receiving RT, the 5- and 10-year IBE rates (5.4 and 14.5%) were higher than the CBE rates (1.8 and 2.7%). Among those receiving RT, the IBE rates (1.5 and 6.0%) were lower than the CBE rates (4.1 and 15.6%). The women receiving RT trended toward significantly lower IBE rates (p = 0.07). Age, grade, and endocrine therapy were not significantly associated with IBE risk. CONCLUSIONS: Among the patients with mDCIS who did not receive RT, the IBE risk was substantially higher than the CBE risk, demonstrating that even DCIS of very low volume is associated with clinically relevant disease. The finding that the IBE risk was greater than the CBE risk supports current strategies that treat DCIS as a precursor rather than a risk marker. Women with mDCIS are not at negligible risk for IBE in the absence of adjuvant therapy.

Fibroepithelial Lesions in the Breast of Adolescent Females: A Clinicopathological Study of 54 Cases.

Fibroepithelial lesions (FELs) are the most frequent breast tumors in adolescent females. The pubertal hormonal surge could impact the growth and microscopic appearance of FELs in this age group. In this study, we evaluate the morphology and clinical behavior of FELs in adolescents. We searched the 1992-2012 pathology data base for FELs in females 18 years old or younger (F ≤18 years). Seven FELs from 1975 to 1983 were also included. Three pathologists reviewed all available material. Patient (pt) characteristics and follow-up information were obtained from electronic medical records. Forty-eight F ≤18 years had 54 FELs with available slides. Thirty (67%) pts were Caucasian, 12 (27%) African-American, two (4%) Hispanic, one (2%) Asian; three were of unknown race/ethnicity. Median age at diagnosis was 16 years. Median age at menarche was 12 years; most (96%) FELs occurred after menarche (median interval 48 months). All patients underwent lumpectomy; one required subsequent mastectomy. The FELs were 34 fibroadenomas (FAs) (11 usual, 23 juvenile), and 20 phyllodes tumors (PTs) (16 benign, one borderline and three malignant). Eight (35%) juvenile FAs showed slight intratumoral heterogeneity. The mean mitotic rate was 1.3 mitoses/10 high-power fields (HPFs) (range, 0-6) in usual FAs, 1.8/10 HPFs in juvenile FAs, 3.1/10 HPFs in benign PTs, 10/10 HPFs in the borderline PT and 17/10 HPFs in malignant PTs. The mean follow-up for 29 pts with 33 FELs was 44 months. Two (10%) PTs recurred locally (a benign PT at 18 months, and a borderline PT at 11 months). Both recurrent PTs had microscopic margins <1 mm. Mitotic activity in FAs from adolescents can be substantial and this finding should be interpreted cautiously. Awareness of the morphologic features of FELs in adolescents is important to avoid overdiagnosis of PTs, which can lead to additional unnecessary and potentially disfiguring surgery.

Atypical Ductal Hyperplasia Bordering on Ductal Carcinoma In Situ.

BACKGROUND: The clinical implications of the diagnosis of atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) are very different. Yet there are "borderline" breast lesions that have characteristics of both ADH and DCIS. We examined interobserver diagnostic variability for such lesions and correlated pathologic features of the lesions with clinical outcomes. METHODS: We identified all cases of borderline ADH/DCIS lesions treated at our center from 1997 to 2010. Five specialized breast pathologists blinded to clinical outcomes independently reviewed all available slides from each case and were instructed to classify each as benign, ADH, or DCIS. A majority diagnosis (MajDx) was defined as a diagnosis agreed upon by ≥3 pathologists. RESULTS: A total of 105 women with borderline ADH/DCIS and slides available for review were identified. The MajDx was ADH in 84 (80%), and DCIS in 18 (17%). There were split diagnoses in 3 (3%). MajDx of DCIS correlated significantly with lesion size and nuclear grade. There was diagnostic agreement by all 5 pathologists in 30% of cases, 4 pathologists in 42%, and 3 pathologists in 25%. At a median follow-up of 37 months, 4 (3.8%) patients developed subsequent ipsilateral breast carcinoma (2 invasive, 2 DCIS); all 4 cases had MajDx of ADH. CONCLUSIONS: Borderline ADH/DCIS represents an entity for which reproducible categorization as ADH or DCIS cannot be achieved. Furthermore, histologic features of borderline lesions resulting in MajDx of ADH vs. DCIS are not prognostic for risk of subsequent breast carcinoma.

Women with Low-Risk DCIS Eligible for the LORIS Trial After Complete Surgical Excision: How Low Is Their Risk After Standard Therapy?

BACKGROUND: Identifying DCIS patients at low risk for disease progression could obviate need for standard therapy. The LORIS (surgery versus active monitoring for low-risk DCIS) trial is studying the safety of monitoring low-risk DCIS, although ipsilateral breast tumor recurrence (IBTR) rates in patients meeting enrollment criteria after complete surgical excision are unknown. METHODS: Women with pure DCIS treated with breast-conserving surgery (BCS) with/without radiation therapy (RT) from 1/1996-1/2011 were included from a prospectively maintained database. IBTR rates were compared between those who did and did not meet LORIS eligibility criteria (age ≥ 46 years, screen-detected calcifications, nipple discharge absence, minimal family history, non-high-grade DCIS) after complete surgical excision. RESULTS: A total of 2394 women were identified; 401 met LORIS criteria. Median follow-up was 5.9 years; 431 had ≥10 years follow-up. LORIS cohort median age was 61 years (range 46-86 years); 207 (52 %) underwent RT, 79 (20 %) received endocrine therapy. Of 401 patients, 24 experienced an IBTR. Overall 10-year IBTR rates were 10.3 % (LORIS) versus 15.4 % (non-LORIS) (p = 0.08); without RT, 12.1 versus 21.4 %, respectively (p = 0.06). The 10-year invasive-IBTR rates for women meeting LORIS criteria were: 5.3 % BCS overall, 6.0 % without RT. CONCLUSIONS: Women meeting LORIS criteria (after complete surgical excision) are at somewhat lower risk for IBTR. Among such women undergoing excision without RT, the 10-year invasive-IBTR rate was 6 %. Given that approximately 20 % of women with core biopsy-proven non-high-grade DCIS have invasive cancer at excision, women managed without excision would be expected to incur higher invasive cancer rates. Additional criteria are needed to identify women not requiring intervention for DCIS.

Impact of Age on Risk of Recurrence of Ductal Carcinoma In Situ: Outcomes of 2996 Women Treated with Breast-Conserving Surgery Over 30 Years.

BACKGROUND: Age is a known risk factor for recurrence in women with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS). We explored the relationship between age, other risk factors, and recurrence. METHODS: Using a prospectively maintained database of DCIS patients undergoing BCS from 1978 to 2010, the association of age and recurrence risk was analyzed using Kaplan-Meier estimates, multivariable analysis, and competing risk multivariable analysis. RESULTS: Overall, 2996 cases were identified. Median follow-up for those without recurrence was 75 months; 732 were followed for ≥10 years, and 363 (12 %) had recurrence [192 (53 %) DCIS, 160 (44 %) invasive, 11 (3 %) unknown]. Risk of recurrence decreased with age, even after adjustment for eight clinicopathologic variables on multivariable analysis [hazard ratios (HR), with <40 years of age as the reference: 40-49 years, 0.82 (p = 0.36), 50-59 years, 0.46 (p = 0.0005), 60-69 years, 0.50 (p = 0.003), 70-79 years, 0.56 (p = 0.02), ≥80 years, 0.21 (p = 0.0015)]. This association persisted for cohorts with and without radiation therapy. Using competing risk multivariable analysis, the effect of age on invasive recurrence was empirically stronger than for DCIS recurrence. Ten-year invasive recurrence was 16 and 6.5 % in women <40 years of age and women ≥40 years of age, respectively. Only 0.6 % of the population ultimately developed distant disease; those <40 years of age constituted 4.7 % (141/2996) of the population, but 21 % (4/19) of those developed distant disease. CONCLUSIONS: The risk of recurrence of DCIS decreases with age. This effect is particularly strong at the extremes of age and is independent of other clinicopathologic factors. The oldest women are at low risk of recurrence, while the youngest women have a higher overall, and especially invasive, recurrence rate, although mortality remains low. These findings should be incorporated into risk/benefit discussions of treatment options.

Fertility Preservation for the Young Breast Cancer Patient.

BACKGROUND: The American Society of Clinical Oncology (ASCO) guidelines include incorporation of fertility preservation guidelines in the care of breast oncology patients. This study aimed to examine the baseline knowledge and preferences concerning fertility preservation among women of childbearing age with newly diagnosed breast cancer at the time of their initial visit to Memorial Sloan Kettering Cancer Center (MSKCC). METHODS: A questionnaire on reproductive history, fertility knowledge, and preservation options was administered to women 18-45 years of age with newly diagnosed breast cancer at MSKCC between May and September 2011. RESULTS: The inclusion criteria were met by 60 women eligible for analysis who had a median age of 40 years (range 20-45 years). The findings showed that 50 % of the women either desired children in the future or were unsure whether they wanted children, with 9 % reporting that they received information about fertility preservation options before their MSKCC visit. Women who had never been pregnant were more likely than those with prior pregnancies to consider having children in the future (p = 0.001) and to contemplate fertility preservation options both before (p = 0.001) and after (p = 0.0002) cancer treatment. CONCLUSION: Early referral allows patients to take advantage of fertility preservation options while preventing delay in the initiation of systemic therapy. Referral by the breast surgical oncologist at the time of the initial visit has the potential to increase fertility knowledge because it appears that many women have not yet received fertility information at this early treatment stage.

Relationship Between Margin Width and Recurrence of Ductal Carcinoma In Situ: Analysis of 2996 Women Treated With Breast-conserving Surgery for 30 Years.

OBJECTIVE: Our goal was to investigate, in a large population of women with ductal carcinoma in situ (DCIS) and long follow-up, the relationship between margin width and recurrence, controlling for other characteristics. BACKGROUND: Although DCIS has minimal mortality, recurrence rates after breast-conserving surgery are significant, and half are invasive. Positive margins are associated with increased risk of local recurrence, but there is no consensus regarding optimal negative margin width. METHODS: We retrospectively reviewed a prospective database of DCIS patients undergoing breast-conserving surgery from 1978 to 2010. Univariate and Cox proportional hazard models were used to investigate the association between margin width and recurrence. RESULTS: In this review, 2996 cases were identified, of which 363 recurred. Median follow-up for women without recurrence was 75 months (range 0-30 years); 732 were studied for ≥10 years. Controlling for age, family history, presentation, nuclear grade, number of excisions, radiotherapy (RT), endocrine therapy, and year of surgery, margin width was significantly associated with recurrence in the entire population. Larger negative margins were associated with a lower hazard ratio compared with positive margins. An interaction between RT and margin width was significant (P < 0.03); the association of recurrence with margin width was significant in those without RT (P < 0.0001), but not in those with RT (P = 0.95). CONCLUSIONS: In women not receiving RT, wider margins are significantly associated with a lower rate of recurrence. Obtaining wider negative margins may be important in reducing the risk of recurrence in women who choose not to undergo RT and may not be necessary in those who receive RT.

Decreasing Recurrence Rates for Ductal Carcinoma In Situ: Analysis of 2996 Women Treated with Breast-Conserving Surgery Over 30 Years.

BACKGROUND: Randomized trials of radiation after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) found substantial rates of recurrence, with half of the recurrences being invasive. Decreasing local recurrence rates for invasive breast carcinoma have been observed and are largely attributed to improvements in systemic therapy. In this study, we examine recurrence rates after BCS for DCIS over 3 decades at one institution. METHODS: We retrospectively reviewed a prospectively maintained database of DCIS patients undergoing BCS from 1978 to 2010. Cox proportional hazard models were used to investigate the association between the treatment period and recurrence, controlling for other variables. RESULTS: Overall, 363 (12%) recurrences among 2996 cases were observed. Median follow-up for patients without recurrence was 75 months (range 0-30 years); 732 patients were followed for ≥10 years. The 5-year recurrence rate for the period 1978-1998 was 13.6 versus 6.6% for the period 1999-2010 [hazard ratio (HR) 0.62, p < 0.0001]. Controlling for age, family history, presentation, nuclear grade, necrosis, number of excisions, margin status, radiation, and endocrine therapy, treatment period remained significantly associated with recurrence, with later years associated with a lower HR (0.74, p = 0.02) compared to earlier. After stratification by radiation use, association of recurrence with treatment period persisted in those treated without radiation (HR 0.62, p = 0.003). CONCLUSIONS: Recurrence rates for DCIS have fallen over time, with increases in screen detection, negative margins, and use of adjuvant therapies only partially explaining this decrease. The unexplained decline persists in women not receiving radiation, suggesting it is not due to changes in radiation efficacy but may be due to improvements in radiologic detection and pathologic assessment.

Perioperative breast MRI is not associated with lower locoregional recurrence rates in DCIS patients treated with or without radiation.

INTRODUCTION: For women with ductal carcinoma in situ (DCIS) undergoing breast-conserving surgery (BCS), the benefit of magnetic resonance imaging (MRI) remains unknown. Here we examine the relationship of MRI and locoregional recurrence (LRR) and contralateral breast cancer (CBC) for DCIS treated with BCS, with and without radiotherapy (RT). METHODS: A total of 2,321 women underwent BCS for DCIS from 1997 to 2010. All underwent mammography, and 596 (26 %) also underwent perioperative MRI; 904 women (39 %) did not receive RT, and 1,391 (61 %) did. Median follow-up was 59 months, and 548 women were followed for ≥8 years. The relationship between MRI and LRR was examined using multivariable analysis. RESULTS: There were 184 LRR events; 5- and 8-year LRR rates were 8.5 and 14.6 % (MRI), respectively, and 7.2 and 10.2 % (no-MRI), respectively (p = 0.52). LRR was significantly associated with age, menopausal status, margin status, RT, and endocrine therapy. After controlling for these variables and family history, presentation, number of excisions, and time period of surgery, there remained no trend toward association of MRI and lower LRR [hazard ratio (HR) 1.18, 95 % confidence interval (CI) 0.79-1.78, p = 0.42]. Restriction of analysis to the no-RT subgroup showed no association of MRI with lower LRR rates (HR 1.36, 95 % CI 0.78-2.39, p = 0.28). No difference in 5- or 8-year rates of CBC was seen between the MRI (3.5 and 3.5 %) and no-MRI (3.5 and 5.1 %) groups (p = 0.86). CONCLUSIONS: We observed no association between perioperative MRI and lower LRR or CBC rates in patients with DCIS, with or without RT. In the absence of evidence that MRI improves outcomes, the routine perioperative use of MRI for DCIS should be questioned.

Impact of margin assessment method on positive margin rate and total volume excised.

BACKGROUND: For breast-conserving surgery, the method of margin assessment that most frequently achieves negative margins without increasing the volume of tissue excised is uncertain. We examined our institutional experience with three different margin assessment methods used by six experienced breast surgeons. METHODS: Patients undergoing breast-conserving surgery for invasive carcinoma during July to December of a representative year during which each method was performed (perpendicular, 2003; tangential, 2004; cavity shave, 2011) were included. The effect of margin method on the positive margin rate at first excision and the total volume excised to achieve negative margins were evaluated by multivariable analysis, by surgeon, and by tumor size and presence of extensive intraductal component (EIC). RESULTS: A total of 555 patients were identified, as follows: perpendicular, 140; tangential, 124; and cavity shave, 291. The tangential method had a higher rate of positive margins at first excision than the perpendicular and cavity-shave methods (49, 15, 11 %, respectively; p < 0.0001). Median volumes to achieve negative margins were similar (55 ml perpendicular; 64 ml tangential; 62 ml cavity shave; p = 0.24). Four of six surgeons had the lowest rate of positive margins with the cavity-shave method, which was significant when compared to the tangential method (p < 0.0001) but not the perpendicular method (p = 0.37). The volume excised by the three methods varied by surgeon (p < 0.0001). The perpendicular method was optimal for T1 tumors without EIC; the cavity-shave method tended to be superior for T2-T3 tumors and/or EIC. CONCLUSIONS: Although the cavity-shave method may decrease the rates of positive margins, its effect on volume is variable among surgeons and may result in an increase in the total volume excised for some surgeons and for small tumors without EIC.

Blurry boundaries: do epithelial borderline lesions of the breast and ductal carcinoma in situ have similar rates of subsequent invasive cancer?

BACKGROUND: The histology of epithelial "borderline lesions" of the breast, which have features in between atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS), is well described, but the clinical behavior is not. This study reports subsequent ipsilateral breast events (IBE) in patients with borderline lesions compared with those with DCIS. METHODS: Patients undergoing breast-conserving surgery for borderline lesions or DCIS from 1997 to 2010 were identified from a prospective database. IBE was defined as the diagnosis of subsequent ipsilateral DCIS or invasive ductal carcinoma. RESULTS: A total of 143 borderline-lesion patients and 2,328 DCIS patients were identified. Median follow-up was 2.9 and 4.4 years, respectively. 7 borderline-lesion and 172 DCIS patients experienced an IBE. 5 year IBE rates were 7.7 % for borderline lesions and 7.2 % for DCIS (p = .80). 5 year invasive IBE rates were 6.5 and 2.8 %, respectively (p = .25). Similarly, when analyses were restricted to patients who did not receive radiotherapy, or endocrine therapy, or both, borderline-lesion and DCIS patients did not demonstrate statistically significant differences in rates of IBE or invasive IBE. CONCLUSIONS: When compared with DCIS, borderline lesions do not demonstrate lower rates of IBE or invasive IBE. Despite "borderline" histology, a 5 year IBE rate of 7.7 % and an invasive IBE rate of 6.5 % suggest that the risk of future carcinoma is significant and similar to that of DCIS.