The Association Between Breast Cancer Predisposing Genetic Variants and Multifocal, Multicentric Breast Cancer.

BACKGROUND: Breast-conserving surgery is often discouraged in BRCA gene carriers with early onset breast cancer. The genetic variant carrier breast cancers are more likely to be multifocal or multicentric (MFMC). PATIENTS AND METHOD: This retrospective study includes newly diagnosed patients with breast cancer undergoing genetic testing between 2010 and 2021 within the Johns Hopkins Regional Health System. After excluding patients who received neoadjuvant chemotherapy or stage IV breast cancers, patients were divided into two groups: those who tested positive for a variant recognized by the National Comprehensive Cancer Network as predisposing the patient to breast cancer (ATM, BRCA1, BRCA2, CHEK2, NF1, PALB2, RAD51C, RAD51D, and TP53) and those who tested negative. Pathologic features of the tumors were compared, focusing on evidence for MFMC disease, defined as more than one malignant foci more than 5 mm apart. RESULTS: Among the 282 eligible cases, 69 (24%) were positive for a genetic variant. The variant carriers were younger at diagnosis (p < 0.001), more likely to have invasive ductal carcinoma (p = 0.03), more likely to have undergone mastectomy (p = 0.03), and more likely to have a grade 3 cancer (p = 0.003). Variant carriers were not more likely to have MFMC disease (28% vs. 22%, p = 0.4). A positive genetic variant was not a predictor of MFMC within the entire cohort [odds ratio (OR):1.3, 95% confidence interval (CI) 0.6-2.6, p = 0.5). CONCLUSION: Genetic variant carrier cancers are not more likely to be MCMF than sporadic cancers.

Impact of axillary surgery on outcome of clinically node positive breast cancer treated with neoadjuvant chemotherapy.

PURPOSE: Axillary Lymph Node Dissection (ALND) is recommended for breast cancer patients who present with clinically node positive disease (cN1) especially if they have residual nodal disease (ypN+) following neoadjuvant therapy (NAT). It is unknown whether axillary dissection improves outcome for these patients. METHODS: A prospectively maintained database was used to identify all patients who were diagnosed with cTis-T4N1M0 breast cancer treated with NAT. RESULTS: In our study, of 292 cN1 breast cancer patients who received NAT, we compared ALND with targeted axillary surgery (TAS) in ypN+ patients. ALND was performed in 75% of the ypN+ subgroup, while 25% underwent TAS. Axillary recurrence occurred in four ALND patients, but no recurrence was observed in the TAS group (p = 0.21). Five-year axillary recurrence-free survival was 100% for TAS and 90% for ALND (p = 0.21). Overall survival at five years was 97% for TAS and 85% for ALND (p = 0.39). Disease-free survival rates at five years were 51% for TAS and 61% for ALND (p = 0.9). Clinicopathological variables were similar between the groups, although some differences were noted. ALND patients had smaller clinical tumor size, larger pathological tumor size, more lymph nodes retrieved, larger tumor deposits, higher rates of extranodal extension, and greater prevalence of macrometastatic nodal disease. Tumor subtype and size of lymph node tumor deposit independently predicted survival. CONCLUSION: Axillary recurrence is infrequent in cN1 patients treated with NAT. Our study found that ALND did not reduce the occurrence of axillary recurrence or enhance overall survival. It is currently uncertain which patients benefit from axillary dissection.

Adjuvant treatment decisions among adults aged 65 years and older with early-stage hormone receptor positive breast cancer seen in a simple multidisciplinary clinic versus standard consultation.

INTRODUCTION: Randomized studies support de-escalation of adjuvant therapy for a target population of older adults ≥65 years with stage I, estrogen-receptor (ER) positive breast cancer after breast conserving surgery. We sought to evaluate the impact of a simplified multidisciplinary clinic (s-MDC) in this population by comparing treatment patterns and patient perceptions of adjuvant radiation therapy (RT) and hormone therapy (HT) between patients seen in s-MDC vs. standard consultations. MATERIALS AND METHODS: Medical records were retrospectively reviewed for patients in the above target population who underwent surgery between August 2020 and May 2022 at our institution. Two cohorts were included: (1) patients seen in s-MDC, and (2) patients seen in standard clinic separately by medical and radiation oncology (non-s-MDC cohort). The non-s-MDC patients declined, could not attend, and/or were not referred to the s-MDC. Patients in the s-MDC cohort were prospectively administered validated questionnaires to evaluate patient reported data including the Decision Autonomy Preference Scale (DAPS), e-Prognosis, and Medical Maximizing-Minimizing Scale (MMS). Chi square, t-tests, and non-parametric equivalents compared demographics, and logistic regression evaluated RT and HT use and survey score outcomes between cohorts. RESULTS: A total of 127 patients met inclusion criteria, with 33 s-MDC and 94 non-s-MDC patients. There was no difference between the cohorts in age, margin status, histology, grade, or focality. In the s-MDC cohort there were significantly more patients without sentinel lymph node biopsy (71.3% vs 42.4%, p = 0.003) and mean tumor size was smaller (0.69 vs. 0.96 cm, p < 0.003), and Charlson comborbidity index (CCI) was higher (5.21 vs 4.96, p = 0.038). There was no significant difference in receipt of RT (65% s-MDC vs 77% standard; odds ratio [OR] = 0.55, p = 0.189), HT (78% ss-MDC vs 72% standard; OR = 1.36, p = 0.513), or both (50% s-MDC vs 59% standard; OR = 0.7, p = 0.429). The s-MDC cohort was significantly more likely to undergo accelerated (vs. standard hypofractionated) RT (70% vs 39%; OR = 3.59, p = 0.020). In s-MDC patients with completed questionnaires (n = 33), all whose selected "mostly patient (n=6)" based decision making by DAPS chose RT while all "mostly doctor (n=1)" chose no RT. Based on e-Prognosis, there were lower odds of RT for increasing Schonberg score/ higher 10 yr mortality risk (OR 0.600, p = 0.048). MMS score ≥ 40 ("maximizer") was strongly linked with the use of RT (OR 18.57, p = 0.011). DISCUSSION: For adults ≥65 years with early stage, ER positive breast cancer, s-MDC participation was not significantly associated with lower use of adjuvant RT or HT versus standard consultation but was significantly associated with shorter RT courses. DAPS and MMS results indicate that patient treatment preference may be predictable, highlighting an opportunity to tailor consultation discussions and recommendations based on intrinsic patient preferences and individual goals.

Ultrasound-Based Nomogram Identifies Breast Cancer Patients Unlikely to Harbor Axillary Metastasis: Towards Selective Omission of Sentinel Lymph Node Biopsy.

BACKGROUND: As tumor biology takes precedence over anatomic staging to determine breast cancer (BC) prognosis, there is growing interest in limiting axillary surgery. There is a need for tools to identify patients at the lowest risk of harboring axillary lymph node (ALN) disease, to determine when omission of sentinel lymph node biopsy (SLNB) may be appropriate. We examined whether a nomogram using preoperative axillary ultrasound (axUS) findings, clinical tumor size, receptor status, and grade to calculate the probability of nodal metastasis (PNM) has value in surgical decision making. METHODS: This was a retrospective analysis of female patients (February 2011-October 2014) with invasive BC who underwent preoperative axUS and axillary surgery. Cases with locally advanced BC, neoadjuvant treatment, or bilateral BC were excluded. PNM was calculated for each case. Using various PNM thresholds, the proportion of cases with ALN metastasis on pathology was examined to determine an optimal PNM cut-point to predict ALN negativity. RESULTS: Of 357 included patients, 72% were node-negative on surgical staging, and 69 (19.6%) had a PNM < 9.3%. Of these 69 patients, 6 had ALN metastasis on surgical pathology, yielding a false negative rate (FNR) of 8.7% for predicting negative ALN when a PNM threshold of < 9.3% was used. CONCLUSION: A nomogram incorporating axUS findings and tumor characteristics identified a sizeable subgroup (19.6%) in whom ALN was predicted to be negative, with an 8.7% FNR. Surgeons can use this nomogram to quantify the probability of ALN metastasis and select patients who may benefit from omitting SLNB.

Papillary Breast Lesions: Association with Malignancy and Upgrade Rates on Surgical Excision.

Intraductal papilloma falls under the category of benign breast mass. However, recent studies show that it can harbor occult carcinoma. The management of benign intraductal papilloma remains controversial because of its nonspecific radiologic and histological findings, as well as its association with surrounding malignant pathology. The purpose of this study is to investigate upgrade rates of a benign intraductal papilloma on surgical excision and the need for surgical excision of papillary lesions diagnosed at core needle biopsy. A retrospective review of a single institution's pathology database between 2011 and 2015 identified 43 core biopsies with benign papilloma. We followed the upgrade rates of these lesions on surgical excision. There were 90 biopsies with the diagnosis of benign intraductal papilloma. The average age was 55.2 (range from 24-87 years old). Forty-three had benign intraductal papilloma; 28 of the 43 core biopsies had surgical excision. Two (7.1%) had an upgrade from benign intraductal papilloma to intraductal papilloma with atypia. One (3.6%) had an upgrade to ductal carcinoma in situ. None had invasive cancer. Surgical findings were in agreement with core biopsies in 25 (89.3%) of 28 cases (κ = 0.80, P < 0.0001). Core biopsies have a statistically significant correlation with pathologies on surgical excision in detecting atypia in breast lesion as demonstrated by κ = 0.80. However, the study shows benign intraductal papillomas on core biopsy have an upgrade rate of 10.7 per cent after undergoing surgical excision. As such, we recommend a more aggressive approach including surgical excision of all benign intraductal papillary lesions.

Positive Ultrasound-guided Lymph Node Needle Biopsy in Breast Cancer may not Mandate Axillary Lymph Node Dissection.

BACKGROUND: The ACOSOG Z0011 (Z11) trial demonstrated that in patients with nonpalpable axillary lymph nodes (LN) and one to two positive sentinel LN (SLN), axillary LN dissection (ALND) is unnecessary.JAMA 305:569-575, [2011], Ann Surg 264:413-42, [2016] The Z11 trial did not require preoperative axillary ultrasound (axUS). In many centers, preoperative axUS is part of the standard workup of a newly diagnosed breast cancer patient, but in light of the Z11 results, its role is now questioned. METHODS: We retrospectively analyzed newly diagnosed breast cancer patients at two institutions. Inclusion criteria were patients with (1) no palpable lymphadenopathy, (2) abnormal axUS, (3) axillary LN metastasis confirmed preoperatively by axUS-lymph node needle biopsy, (4) no neoadjuvant therapy, and (5) ALND. LN disease burden was dichotomized as N1 versus N2-3. We examined relationships between clinicopathologic factors, including axUS characteristics, and LN disease burden. RESULTS: Of 129 included cases, 67 had N1 disease (51.9%) and 62 had N2-3 disease (48.1%). Factors significantly associated with N1 disease were tumor size ≤2 cm (p = 0.012), nonlobular histology (p = 0.013), and one suspicious LN on axUS (p = 0.008). For patients with both tumor size on imaging ≤2 cm and one abnormal LN on axUS, only 27% had N2-3 disease (p = 0.007). CONCLUSIONS: More than half of patients without palpable adenopathy but with preoperative US-guided biopsy proven axillary LN metastases had N1 disease. For patients with both tumor size ≤2 cm and only 1 abnormal LN on axUS, 73% had N1 disease. This suggests that such patients, if they are otherwise analogous to Z11 patients, may undergo attempt at SLNB.