The optimal method for locoregional staging in patients treated with neoadjuvant chemotherapy (NAC), usually ultrasound (US) and pre- or post-chemotherapy sentinel lymph node biopsy (SLNB), remains ...subject of debate. The aim of this study was to assess the value of 18F-FDG PET/CT for detecting locoregional lymph node metastases in primary breast cancer patients scheduled for NAC. 311 breast cancer patients, scheduled for NAC, underwent PET/CT of the thorax in prone position with hanging breasts. A panel of four experienced reviewers examined PET/CT images, blinded for other diagnostic procedures. FDG uptake in locoregional nodes was determined qualitatively using a 4-point scale (0 = negative, 1 = questionable, 2 = moderately intense, and 3 = very intense). Results were compared with pathology obtained by US-guided fine needle aspiration or SLNB prior to NAC. All FDG-avid extra-axillary nodes were considered metastatic, based on the previously reported high positive predictive value of the technique. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG-avid nodes for the detection of axillary metastases (score 2 or 3) were 82, 92, 98, 53, and 84 %, respectively. Of 28 patients with questionable axillary FDG uptake (score 1), 23 (82 %) were node-positive. Occult lymph node metastases in the internal mammary chain and periclavicular area were detected in 26 (8 %) and 32 (10 %) patients, respectively, resulting in changed regional radiotherapy planning in 50 (16 %) patients. In breast cancer patients scheduled for NAC, PET/CT renders pre-chemotherapy SLNB unnecessary in case of an FDG-avid axillary node, enables axillary response monitoring during or after NAC, and leads to changes in radiotherapy for a substantial number of patients because of detection of occult N3-disease. Based on these results, we recommend a PET/CT as a standard staging procedure in breast cancer patients scheduled for NAC.
In breast cancer patients treated with neoadjuvant chemotherapy (NAC) the number of tumor-positive nodes can no longer reliably be determined. Furthermore, ultrasound (US) seems suboptimal for the ...detection of N3-disease. Therefore we assessed the proportion of breast cancer patients treated with NAC in which pre-chemotherapy 18F-FDG PET/CT detected ≥4 axillary nodes or occult N3-disease, upstaging nodal status and changing risk estimation for locoregional recurrence (LRR). Conventional regional staging consisted of US with fine needle aspiration and/or sentinel lymph node biopsy. Patients were classified as low-risk (cT2N0), intermediate-risk (cT0N1, cT1N1, cT2N1, cT3N0), or high-risk (cT3N1, cT4, cN2–3) for LRR. The presence and number of FDG-avid nodes were evaluated and the proportion of patients that would be upstaged by PET/CT, based on detection of ≥4 FDG-avid axillary nodes defined as cN2(4+) or occult N3-disease, was calculated. In total, 87 of 278 patients were considered high-risk based on conventional staging. PET/CT detected occult N3-disease in 5 (11 %) of 47 low-risk patients. In 144 intermediate-risk patients, PET/CT detected ≥4 FDG-avid nodes in 24 (17 %) patients and occult N3-disease in 22 (15 %) patients, thereby finally upstaging 38 (26 %) of intermediate-risk patients. Of 43 (23 %) upstaged patients, 18 were ypN0, 12 were ypN1, and 13 were ypN2–3. Pre-chemotherapy PET/CT is valuable for selection of breast cancer patients at high risk for LRR. In our population, 23 % of patients treated with NAC were upstaged to the high-risk group based on PET/CT information, potentially benefiting from regional radiotherapy.
Introduction
Breast cancer patients with invasive lobular carcinoma (ILC) have an increased risk of positive margins after surgery and often show little response to neoadjuvant chemotherapy (NAC). We ...aimed to investigate surgical outcomes in patients with ILC treated with NAC.
Methods
In this retrospective cohort study, all breast cancer patients with ILC treated with NAC who underwent surgery at the Netherlands Cancer Institute from 2010 to 2019 were selected. Patients with mixed type ILC in pre-NAC biopsies were excluded if the lobular component was not confirmed in the surgical specimen. Main outcomes were tumor-positive margins and re-excision rate. Associations between baseline characteristics and tumor-positive margins were assessed, as were complications, locoregional recurrence rate (LRR), recurrence-free survival (RFS), and overall survival (OS).
Results
We included 191 patients. After NAC, 107 (56%) patients had breast conserving surgery (BCS) and 84 (44%) patients underwent mastectomy. Tumor-positive margins were observed in 67 (35%) patients. Fifty five (51%) had BCS and 12 (14%) underwent mastectomy (
p
value < 0.001). Re-excision was performed in 35 (33%) patients with BCS and in 4 (5%) patients with mastectomy. Definitive surgery was mastectomy in 107 (56%) patients and BCS in 84 (44%) patients. Tumor-positive margins were associated with cT ≥ 3 status (OR 4.62, 95% CI 1.26–16.98,
p
value 0.021) in the BCS group. Five-year LRR (4.7%), RFS (81%), and OS (93%) were not affected by type of surgery after NAC.
Conclusion
Although 33% of ILC breast cancer patients undergoing BCS after NAC required re-excision for positive resection margins, it is considered safe given that five-year RFS remained excellent and LRR and OS did not differ by extent of surgery.
Developing algorithms for analyzing hyperspectral images as an intraoperative tool for margin assessment during breast-conserving surgery requires a dataset with reliable histopathologic labels. The ...feasibility of using tissue slices hyperspectral dataset with a high correlation with histopathology for developing an algorithm for analyzing the images from the surface of lumpectomy specimens was investigated. We presented a method to acquire hyperspectral images from the lumpectomy surface with a high correlation with histopathology. The tissue slices dataset was compared with the dataset obtained on lumpectomy specimen and the wavelengths with a penetration depth up to the minimum sample thickness of the tissue slices were used to develop a tissue classification algorithm. Spectral differences were observed between tissue slices and lumpectomy datasets due to differences in the sample thickness between both datasets; wavelengths with a high penetration depth were able to penetrate through the thinner tissue slices, affecting the captured signal. By using only wavelengths with a penetration depth up to the minimum sample thickness of the tissue slices, the adipose tissue could be discriminated from other tissue types, but differentiating malignant from connective tissue was more challenging.
Background
Radioguided occult lesion localization (ROLL) with technetium-99 m colloid (ROLL-
99m
Tc) is commonly used to perform breast-conserving surgery in patients with nonpalpable breast tumors. ...Radioactive seed localization is a relatively new technique that localizes the tumor with a radioactive iodine-125 (
125
I) seed. The feasibility and outcome of these techniques after neoadjuvant systemic treatment has not been widely investigated.
Methods
All patients treated with neoadjuvant systemic treatment between 2007 and 2010 in the Netherlands Cancer Institute who underwent breast-conserving surgery with the ROLL-
99m
Tc technique (
n
= 83) or with
125
I seed localization (
n
= 71) were analyzed. The weight of the resected specimen, the margins, and the percentage of patients requiring a second surgical intervention as a result of positive margins were assessed.
Results
Patient and tumor characteristics and systemic treatment regimens were comparable between both groups. The median weight of the resected specimen (53 vs. 48 g), the median smallest margin (3.5 vs. 3.0 mm), and the risk for additional surgery for incomplete resections (7 vs. 8 %) did not differ significantly between patients treated with the ROLL-
99m
Tc technique and
125
I seed localization.
Conclusions
The ROLL-
99m
Tc technique and
125
I seed localization demonstrate comparable results when used to perform breast-conserving surgery after neoadjuvant systemic treatment. Because
125
I seed localization does not require additional radiological localization shortly before surgery, it simplifies surgery scheduling. Therefore, we prefer
125
I seed localization to perform breast-conserving surgery after neoadjuvant systemic treatment.
: Preoperative localization is important to optimize the surgical treatment of breast lesions, especially in nonpalpable lesions. Radioactive seed localization (RSL) using iodine‐125 is a relatively ...new approach. To provide accurate guidance to surgery, it is important that the seeds do not migrate after placement. The aim of this study was to assess short‐term and long‐term seed migration after RSL of breast lesions. In 45 patients, 48 RSL procedures were performed under ultrasound or stereotactic guidance. In the first 12 patients, the lesion was localized with two markers: an iodine‐125 seed and a reference marker. In 33 patients, 36 RSL procedures were performed using a single iodine‐125 seed. All patients received control mammograms after seed placement and prior to surgery. In the patients with two markers, migration was defined as the difference in the largest distance between the markers observed in the mammograms. For single‐marked lesions, migration was assessed by comparing distances between anatomical landmarks in the mammograms. RSL was successful in all patients. Seeds were in‐situ for 59.5 days on average (3–136 days). The detection rate during surgery was 100%. Overall, an average seed migration of 0.9 mm (standard deviation 1.0 mm) was observed. Neither differences in lesion type, nor days in situ, type of surgery or radiologic localization method were found to have impact on seed migration. RSL is an accurate preoperative localization method for breast lesions with negligible seed migration, independent of time in‐situ.
Background
Neoadjuvant systemic treatment (NST) leads to pathologic complete response (pCR) in 10–89% of breast cancer patients depending on subtype. The added value of surgery is uncertain in ...patients who reach pCR; however, current imaging and biopsy techniques aiming to predict pCR are not accurate enough. This study aims to quantify the residual disease remaining after NST in patients with a favorable response on MRI and residual disease missed with biopsies.
Methods
In the MICRA trial, patients with a favorable response to NST on MRI underwent ultrasound-guided post-NST 14G biopsies followed by surgery. We analyzed pathology reports of the biopsies and the surgical specimens. Primary outcome was the extent of residual invasive disease among molecular subtypes, and secondary outcome was the extent of missed residual invasive disease.
Results
We included 167 patients. Surgical specimen showed residual invasive disease in 69 (41%) patients. The median size of residual invasive disease was 18 mm (interquartile range IQR 12–30) in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) patients, 8 mm (IQR 3–15) in HR+/HER2-positive (HER2+) patients, 4 mm (IQR 2–9) in HR-negative (HR−)/HER2+ patients, and 5 mm (IQR 2–11) in triple-negative (TN) patients. Residual invasive disease was missed in all subtypes varying from 4 to 7 mm.
Conclusion
Although the extent of residual invasive disease is small in TN and HER2+ subtypes, substantial residual invasive disease is left behind in all subtypes with 14G biopsies. This may hamper local control and limits adjuvant systemic treatment options. Therefore, surgical excision remains obligatory until accuracy of imaging and biopsy techniques improve.
Background
The added value of surgery in breast cancer patients with pathological complete response (pCR) after neoadjuvant systemic therapy (NST) is uncertain. The accuracy of imaging identifying ...pCR for omission of surgery, however, is insufficient. We investigated the accuracy of ultrasound-guided biopsies identifying breast pCR (ypT0) after NST in patients with radiological partial (rPR) or complete response (rCR) on MRI.
Methods
We performed a multicenter, prospective single-arm study in three Dutch hospitals. Patients with T1–4(N0 or N +) breast cancer with MRI rPR and enhancement ≤ 2.0 cm or MRI rCR after NST were enrolled. Eight ultrasound-guided 14-G core biopsies were obtained in the operating room before surgery close to the marker placed centrally in the tumor area at diagnosis (no attempt was made to remove the marker), and compared with the surgical specimen of the breast. Primary outcome was the false-negative rate (FNR).
Results
Between April 2016 and June 2019, 202 patients fulfilled eligibility criteria. Pre-surgical biopsies were obtained in 167 patients, of whom 136 had rCR and 31 had rPR on MRI. Forty-three (26%) tumors were hormone receptor (HR)-positive/HER2-negative, 64 (38%) were HER2-positive, and 60 (36%) were triple-negative. Eighty-nine patients had pCR (53%; 95% CI 45–61) and 78 had residual disease. Biopsies were false-negative in 29 (37%; 95% CI 27–49) of 78 patients. The multivariable associated with false-negative biopsies was rCR (FNR 47%; OR 9.81, 95% CI 1.72–55.89;
p
= 0.01); a trend was observed for HR-negative tumors (FNR 71% in HER2-positive and 55% in triple-negative tumors; OR 4.55, 95% CI 0.95–21.73;
p
= 0.058) and smaller pathological lesions (6 mm vs 15 mm; OR 0.93, 95% CI 0.87–1.00;
p
= 0.051).
Conclusion
The MICRA trial showed that ultrasound-guided core biopsies are not accurate enough to identify breast pCR in patients with good response on MRI after NST. Therefore, breast surgery cannot safely be omitted relying on the results of core biopsies in these patients.
Introduction
Lymphatic drainage patterns from the breast have been described in the past. Drainage may change after treatment of a breast or axilla, and this may have implications for lymphatic ...mapping. The aim of this study was to determine the lymphatic drainage patterns in breast cancer patients with a previously treated ipsilateral breast.
Methods
Between January 1999 and November 2008, 115 sentinel node procedures were performed in breast cancer patients who had undergone treatment of the ipsilateral breast in the past. Lymphatic drainage patterns were analyzed based on preoperative lymphoscintigraphy and sentinel lymph node biopsy. Patients were divided into subgroups according to their previous treatment.
Results
Sentinel nodes were found in 84% of the patients: in 81 patients (70%) in the axilla, 43 patients (37%) had drainage to more than one site, and in 18 patients (16%) no drainage was detected. The percentage of drainage outside the axilla was higher than in a series of untreated breast cancer patients from our institution (51% versus 33%,
P
= 0.01). The 16% nonidentification rate was also higher than the 3.1% in patients without previous treatment (
P
= 0.003). Four patients (3.5%) had lymphatic drainage to the contralateral axilla. Twelve patients (10%) had involved sentinel nodes; these were harvested from the contralateral axilla in two of them. No lymph node recurrences were observed during a median follow-up time of 39 months.
Conclusion
Lymphatic mapping yields a lymph node in 84% of breast cancer patients who have undergone previous treatment of the breast. Nonidentification and extra-axillary nodes are more frequently encountered than in patients without treatment of the breast in the past. The finding of involved nodes suggests that sentinel node biopsy improves staging. Long-term follow-up will determine the sensitivity of the procedure in this specific situation.
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