Abstract
Background:
Axillary assessment in breast cancer is key to determining an upfront surgery or neoadjuvant chemotherapy (NAC) approach. We investigated the false-negative rate (FNR) of axillary-node ultrasound-guided core-needle biopsy (US-CNBx) and the surgical management of pN + patients.
Methods:
This single-institution study from 2010 to 2020 included patients with benign findings on US-CNBx and upfront surgery. Statistical analyses were performed via t-tests and chi-squared tests.
Results:
95 axillae met inclusion, 23 were pN+, resulting in a US-CNBx FNR of 24.2 %. pN + patients more frequently had cT2-T3 tumors vs pN0 patients (43.5 % vs 27.8 %, p = 0.03). Of the 23 pN + patients, 9 underwent breast-conserving surgery (BCS) and 14 underwent mastectomy. In those with BCS, 7 had 1–2 positive nodes, 2 had ≥3 nodes; 3 received an ALND. In those with mastectomies, 12 had 1–2 positive nodes, 2 had ≥3 positive nodes; 6 received an ALND.
Conclusion:
In this cohort, US-CNBx had a FNR of 24.2 %. pN + patients had a greater frequency of cT2–cT3 tumors, therefore clinicians should be cognizant of potential occult nodal disease despite negative CNBx when deciding management.
Keywords: Ultrasound-guided core-needle biopsy, Breast cancer, Axillary assessment and management
1. Introduction
Over the last few decades, axillary nodal management for breast cancer has dramatically changed due to novel developments, including the sentinel lymph node biopsy (SLNB) technique, advances in systemic chemotherapy and radiotherapy, and landmark clinical trials supporting surgical axillary de-escalation even in the setting of pathologically node-positive (pN+) disease.1–9 Accurate nodal evaluation at the time of a breast cancer diagnosis is of paramount significance as it allows the multidisciplinary oncology team to tailor individualized oncologic treatments plans based on current clinical treatment paradigms.
Contemporary management for patients with upfront clinically-node positive disease (cN+) often supports a neoadjuvant chemotherapy (NAC) approach; however, this is dependent on staging, clinical tumor markers, and individual patient characteristics.10 The use of NAC allows for downstaging of the cN + axilla in many, particularly those with human epidermal growth factor-2 (HER2) or triple-negative breast cancer (TNBC), as pathological complete response rates continue to increase with improvements in systemic therapy.8 Patients who have a clinically negative axilla (cN0) after NAC are now able to undergo SLNB alone, with or without targeted axillary dissection, and avoid ALND if found to be pathologically node-negative (pN0) - reducing complications and morbidity associated with ALND.1,11 Thus, clinical examination and radiological evaluation of the axillary nodes at the time of diagnosis is increasingly important in determining optimal treatment and sequence of therapy.
Axillary ultrasound is the gold-standard to evaluate the axillary nodal basin for disease.12 Nodes that are deemed abnormal can be sampled via an ultrasound-guided core needle biopsy (US-CNBx) or an ultrasound-guided fine-needle aspiration (US-FNA). Although the diagnostic accuracy of these biopsies is critical for treatment decision-making, there remains variability in their positive and negative predictive values.13,14 Several meta-analyses have been conducted to determine the reliability and effectiveness of US-guided methods; however, the false-negative rate (FNR) is heterogeneous, and series often include both patients who had US-CNBx and US-FNA in a single analysis, wide ranges in the number of samples taken, variable provider training, with most data sourced from single academic centers.13,15
There is little data to directly inform the contemporary FNR of axillary node US-CNBx. This study aimed to 1) determine the FNR of axillary-node US-CNBx in relation to SLNB and/or ALND findings in breast cancer patients who had a clinically suspicious axilla but negative US-CNBx who underwent upfront surgery and 2) to assess surgical axillary nodal management in those found to be pathologically node positive (pN+) at our institution.
2. Methods
A single-institution retrospective cohort study was conducted from January 2010–December 2020 of patients diagnosed with an invasive breast cancer who were age ≥18 years and had operable (non-Stage IV) disease. Study sites included our primary academic clinical cancer center and two community-based sites of practice within our healthcare network. This study was approved by our Institutional Review Board, which granted a waiver of informed consent given the study design. Patients were included in the study if they initially presented with clinically suspicious axillary nodes, determined via imaging and/or provider physical examination, and then underwent pre-operative axillary node US-CNBx, which yielded benign findings followed by upfront surgery with axillary staging (either with SLNB and/or ALND). Exclusionary criteria were those patients who were found to have malignant cells on preoperative axillary-node US-CNBx, those who had an US-FNA, and those who received any form of neoadjuvant systemic therapy (including neoadjuvant endocrine therapy), those who did not undergo axillary surgery staging due to patient age and favorable primary tumor biology, and shared-decision between the patient and the treating clinical team members.16 Patients with metastatic disease and/or inoperable tumors or those who declined recommended surgical intervention were also excluded.
All imaging examinations and pre-operative axillary-node US-CNBx were performed by board-certified breast radiologists, nearly all of whom completed a Breast Imaging Fellowship. Additionally, all SLNB and/or ALND were performed by board-certified surgeons, the majority with fellowship training in Complex General Surgical Oncology or Breast Surgical Oncology. Pathological examination of nodal tissue was performed by board-certified pathologists of whom nearly all had breast pathology subspecialty fellowship-training. A radiological clip is routinely placed in all biopsied nodes at our institution.
Reflex axillary US for patients diagnosed with invasive cancer is not performed at our center except for patients with a highly suspicious breast lesions ≥2 cm in size or those with multifocal or multicentric disease, per our multidisciplinary breast cancer team’s consensus. Outside of this exception, axillary ultrasound is limited for patients with abnormal nodal findings, defined as abnormal nodes seen incidentally on diagnostic and/or screening mammography, breast magnetic resonance imaging (MRI), or palpable adenopathy on clinical examination. During surgery, axillary sentinel lymph node biopsy frozen sections were sent at the discretion of the operating surgeon based on current standard practice and surgeon preference at the time of the patient’s operation.
Thirty-nine (39) variables were examined, including patient demographics, tumor clinicopathological factors, physical clinical examination findings, documented axillary and breast imaging findings, and surgical axillary management. The study cohort was then subdivided based on final permanent surgical pathology findings of the ipsilateral axillary lymph nodes as either pathological node positive (pN+) or pathological node negative (pN0). The FNR was defined by the number of pN + axillae divided by the number of axillae with a negative CNBx. Statistical analysis was performed via t-tests and chi-squared tests with significance predetermined at p < 0.05.
3. Results
Over the 10-year study period, a total of 94 patients met study inclusion criteria. Except for one individual, all had unilateral disease (98.9 %); this led to a total of 95 clinically suspicious axillae (N = 95). Within the study cohort, median age was 53 years (Interquartile Range (IQR) = 20.3) with a median BMI of 27.6 kg/m2 (IQR = 9.0) (Table 1). Most women were non-Hispanic White (80.9 %), had private insurance (69.1 %), all were assigned female at birth, and over half of the cohort had their breast cancer detected via routine screening mammography (56.8 %). Breast tumors were primarily estrogen receptor (ER)-positive (92.6 %), progesterone receptor (PR)-positive (84.2 %), and HER2 negative/non-amplified (90.0 %). Tumors were predominantly luminal A (85.6 %) followed by luminal B (8.9 %), TNBC (4.4 %), and Her2-enriched (1.1 %). Most tumors were clinical-category T1 (cT1) (62.1 %) and were a solitary lesion (68.8 %). The most common reason for performing a dedicated axillary US was for abnormal nodes identified on diagnostic breast US and/or mammogram (Figs. 1 and 2).
Table 1.
Cohort demographics, breast cancer clinicopathologic and treatment variables in adult women diagnosed with operable invasive breast cancer who received an ultrasound guided axillary core-needle biopsy with a negative result at a single-institution from 2010 to 2020.
| Variable |
Overall
|
pN0
|
pN+
|
p-value | |||
|---|---|---|---|---|---|---|---|
| N | (%) | N | (%) | N | (%) | ||
|
| |||||||
| Axilla | 95 | (100.0 %) | 72 | (75.8 %) | 23 | (24.2 %) | |
| Median Patient Age (years) | 53 | – | 54.5 | – | 51 | – | 0.13 |
| Median Patient BMI (kg/m2) | 27.6 | – | 27.4 | – | 28.7 | – | 0.81 |
| Race/Ethnicity (n = 94) | 0.41 | ||||||
| NH White | 76 | (80.9 %) | 58 | (80.6 %) | 18 | (78.3 %) | |
| NH Black | 10 | (10.6 %) | 6 | (8.3 %) | 4 | (17.4 %) | |
| Hispanic | 5 | (5.3 %) | 5 | (6.9 %) | 0 | (0.0 %) | |
| Asian/PI | 2 | (2.1 %) | 2 | (2.8 %) | 0 | (0.0 %) | |
| Other | 1 | (1.1 %) | 1 | (1.4 %) | 0 | (0.0 %) | |
| Insurance Provider (n = 94) | 0.54 | ||||||
| None | 2 | (2.1 %) | 2 | (2.8 %) | 0 | (0.0 %) | |
| Private | 65 | (69.1 %) | 48 | (66.7 %) | 17 | (77.3 %) | |
| Medicaid/Medicare | 27 | (28.7 %) | 22 | (30.6 %) | 5 | (21.7 %) | |
| Sex Assigned at Birth (n = 94) | N/A | ||||||
| Male | 0 | (0.0 %) | 0 | (0.0 %) | 0 | (0.0 %) | |
| Female | 94 | (100.0 %) | 72 | (100.0 %) | 22 | (100.0 %) | |
| Other | 0 | (0.0 %) | 0 | (0.0 %) | 0 | (0.0 %) | |
| Method of Diagnosis | 0.49 | ||||||
| MMG | 54 | (56.8 %) | 41 | (56.9 %) | 13 | (56.5 %) | |
| Physical Exam | 19 | (20.0 %) | 16 | (22.2 %) | 3 | (13.0 %) | |
| Other | 22 | (23.2 %) | 15 | (20.8 %) | 7 | (30.4 %) | |
| ER Status | 0.78 | ||||||
| Positive | 88 | (92.6 %) | 67 | (93.1 %) | 21 | (91.3 %) | |
| Negative | 7 | (7.4 %) | 5 | (6.9 %) | 2 | (8.7 %) | |
| PR Status | 0.12 | ||||||
| Positive | 80 | (84.2 %) | 63 | (87.5 %) | 17 | (73.9 %) | |
| Negative | 15 | (15.8 %) | 9 | (12.5 %) | 6 | (26.1 %) | |
| HER2 Status (n = 90)* | 0.57 | ||||||
| Positive/Amplified | 9 | (10.0 %) | 6 | (9.0 %) | 3 | (13.0 %) | |
| Negative/Nonamplified | 81 | (90.0 %) | 61 | (91.0 %) | 20 | (87.0 %) | |
| Luminal Status (n = 90)* | 0.81 | ||||||
| A | 77 | (85.6 %) | 58 | (86.6 %) | 19 | (82.6 %) | |
| B | 8 | (8.9 %) | 5 | (7.5 %) | 3 | (13.0 %) | |
| Her2-enriched | 1 | (1.1 %) | 1 | (1.5 %) | 0 | (0.0 %) | |
| TNBC | 4 | (4.4 %) | 3 | (4.5 %) | 1 | (4.3 %) | |
| Clinical T Stage | 0.03 | ||||||
| cTis | 6 | (6.3 %) | 6 | (8.3 %) | 0 | (0.0 %) | |
| cT1 | 59 | (62.1 %) | 46 | (63.9 %) | 13 | (56.5 %) | |
| cT1a | 8 | (13.6 %) | 5 | (10.9 %) | 3 | (13.0 %) | |
| cT1b | 21 | (35.6 %) | 16 | (34.8 %) | 5 | (21.7 %) | |
| cT1c | 30 | (50.8 %) | 25 | (54.3 %) | 5 | (21.7 %) | |
| cT2 | 28 | (29.5 %) | 20 | (27.8 %) | 8 | (34.8 %) | |
| cT3 | 2 | (2.1 %) | 0 | (0.0 %) | 2 | (8.7 %) | |
| cT4 | 0 | (0.0 %) | 0 | (0.0 %) | 0 | (0.0 %) | |
| Pathological T Stage | 0.16 | ||||||
| pTis | 4 | (4.2 %) | 4 | (5.5 %) | 0 | (0.0 %) | |
| pT1 | 62 | (65.3 %) | 50 | (69.4 %) | 12 | (52.2 %) | |
| pT1a | 5 | (8.1 %) | 3 | (6.0 %) | 2 | (8.7 %) | |
| pT1b | 25 | (40.3 %) | 22 | (44.0 %) | 3 | (13.0 %) | |
| pT1c | 31 | (50.0 %) | 25 | (5.0 %) | 6 | (26.1 %) | |
| pT2 | 27 | (28.4 %) | 17 | (23.6 %) | 10 | (43.5 %) | |
| pT3 | 2 | (2.1 %) | 1 | (1.4 %) | 1 | (4.3 %) | |
| pT4 | 0 | (0.0 %) | 0 | (0.0 %) | 0 | (0.0 %) | |
| Pathological N Stage | N/A | ||||||
| pN0 | 75 | (78.9 %) | 72 | (100.0 %) | 3 | (13.0 %) | |
| pN1 (mic) | 4 | (4.2 %) | 0 | (0.0 %) | 4 | (17.4 %) | |
| pN1 | 14 | (14.7 %) | 0 | (0.0 %) | 14 | (60.9 %) | |
| pN2 | 2 | (2.1 %) | 0 | (0.0 %) | 2 | (8.7 %) | |
| Multicentric Disease | 0.47 | ||||||
| Yes | 16 | (16.8 %) | 11 | (15.3 %) | 5 | (21.7 %) | |
| No | 79 | (83.2 %) | 61 | (84.7 %) | 18 | (78.3 %) | |
| Multifocal Disease | 0.51 | ||||||
| Yes | 24 | (25.3 %) | 17 | (23.6 %) | 7 | (30.4 %) | |
| No | 71 | (74.7 %) | 55 | (76.4 %) | 16 | (69.6 %) | |
| Number of ipsilateral breast tumors | 0.30 | ||||||
| 1 | 65 | (68.4 %) | 51 | (70.8 %) | 14 | (60.9 %) | |
| 2 | 15 | (15.8 %) | 12 | (16.7 %) | 3 | (13.0 %) | |
| ≥3 | 15 | (15.8 %) | 9 | (12.5 %) | 6 | (26.1 %) | |
| Abnormal nodes on Screening MMG | 0.80 | ||||||
| Normal | 80 | (84.2 %) | 61 | (84.7 %) | 19 | (82.6 %) | |
| Abnormal | 15 | (15.8 %) | 11 | (15.2 %) | 4 | (17.4 %) | |
| Abnormal nodes on MRI (n = 66) | 0.45 | ||||||
| Normal | 21 | (31.8 %) | 14 | (19.2 %) | 7 | (30.4 %) | |
| Abnormal | 45 | (68.2 %) | 34 | (46.6 %) | 11 | (47.8 %) | |
| Number of Abnormal Nodes on Any Imaging | 0.97 | ||||||
| 1 | 59 | (62.1 %) | 45 | (62.5 %) | 14 | (60.9 %) | |
| 2 | 19 | (20.0 %) | 14 | (19.4 %) | 5 | (21.7 %) | |
| ≥3 | 17 | (17.9 %) | 13 | (18.1 %) | 4 | (17.4 %) | |
| Core Biopsy Needle Gauge Size | 0.14 | ||||||
| Median | 18 | 18 | 18 | ||||
| Number of Core Biopsies Taken | |||||||
| Median | 4 | 4 | 4 | 0.07 | |||
| Mean | 3.97 | 4.03 | 3.56 | ||||
| Type of Breast Surgery | 0.25 | ||||||
| Lumpectomy | 47 | (49.5 %) | 38 | (52.8 %) | 9 | (39.1 %) | |
| Mastectomy | 48 | (50.5 %) | 34 | (47.2 %) | 14 | (60.9 %) | |
Key: pN0 = node-negative on surgical pathology; pN+ = node-positive on surgical pathology; MMG = mammography; MRI = breast magnetic resonance imaging; NH = non-Hispanic, ER = estrogen receptor, PR = progesterone receptor, HER2 = human epidermal growth factor receptor-2. The alphabetical breakdown of cT1 and pT1 was not included in chi-square.
Fig. 1.
Modality of initial abnormal lymph node detection resulting in axillary US-CNBx in pathologically positive and negative axillae in adult women diagnosed with operable invasive breast cancer at a single-institution from 2010 to 2020.
Key: US = ultrasound; MMG = mammogram, US/MMG = ultrasound and mammogram, US/MRI = ultrasound and magnetic resonance imaging; MRI = magnetic resonance imaging; pN+= node-positive on surgical pathology; pN0 = node-negative on surgical pathology.
Fig. 2.
Initial modality of abnormal axillary lymph node detection prompting an US-CNBx stratified by pathologically positive and negative axillae in adult women diagnosed with operable invasive breast cancer at a single-institution from 2010 to 2020.
Key: US = ultrasound; MMG = mammogram, US/MMG = ultrasound and mammogram, US/MRI = ultrasound and magnetic resonance imaging; MRI = magnetic resonance imaging; pN+= node-positive on surgical pathology; pN0 = node-negative on surgical pathology.
While 95 axillae had a negative axillary node US-CNBx, 23 (24.2 %) of these axillae were found to be pN + on surgical pathology (FNR = 24.2 %). Three (13.0 %) of these had isolated tumor cells (ITCs) only, 4 (17.4 %) had microscopic axillary metastasis (pN1(mic)), 14 (60.9 %) were pN1, and 2 (8.7 %) were pN2. For the entire cohort, the median number of nodes removed for ALND was 23 (IQR = 9) and the median nodes removed for SLNB was 3 (IQR = 2). Of the pN + axillae, 39.1 % had an ALND and 60.9 % had a SLNB only. In those with pN + disease, the median number of nodes removed for ALND was 23 (IQR = 9) and the median nodes removed for SLNB was 3 (IQR = 2). The two patients who were pN2 had four and five pathologically positive nodes, respectively, found after ALND. Of those with pN + disease, three (12 %) had HER2+ disease: one with ITCs only, one who was pN1, and another who was pN2. Additionally, one pN + patient had TNBC and was pN1. Over the ten-year study period, 57.9 % of patients in this cohort had an intraoperative frozen section sent on their SLN(s).
Patients with pN + disease more frequently had cT2 or cT3 tumors compared to those who were pN0 (43.5 % vs 27.8 %, p = 0.03). There was insufficient evidence that the mean number of biopsy cores resulted in a lower frequency of positive axillary lymph nodes after negative USCNBs (mean of 4 vs 3.5 cores p = 0.07). There were no statistically significant demographic factors between those who were found to be pN0 or pN+ (Table 1).
Of the 23 pN + axillae, only 17.4 % had documented clinically palpable lymph nodes at the time of diagnosis. Regarding imaging findings of the 23 pN + axillae, abnormal lymph nodes were detected on mammography in 15 (65.2 %), and 18 of the 23 had a breast MRI of which, 11 (47.8 %) detected abnormal nodes. (Table 1). In contrast, of the 72 pN0 axillae, only 8 (11.1 %) had clinically palpable lymph nodes at the time of diagnosis. Regarding imaging findings of the 72 pN0 axillae, abnormal lymph nodes were detected on mammography in 37 (51.4 %), and 48 of the 72, had a breast MRI of which, 34 (70.8 %) detected abnormal nodes.
In terms of primary breast surgical management in the 23 pN + axillae, 9 (39.1 %) underwent breast conserving surgery (BCS) and 14 (60.9 %) underwent mastectomy (Fig. 3). In patients who had BCS, 7 (77.8 %) had 1–2 positive nodes and 2 (22.2 %) had ≥3 nodes. Three of the BCS patients received an ALND each with 2, 3, and 4 positive nodes, respectfully. In patients who underwent mastectomy (n = 14), 12 had 1–2 positive nodes, 1 had ≥3 positive nodes, and another had 5 positive nodes. Six of the mastectomy patients received ALND, of which, 1 had 1 positive node, 3 had 2 positive nodes, 1 had ≥3 positive nodes, and another had 5 positive lymph nodes. All 23 patients with pN + disease had an initial SLNB, and 16 (72.7 %) were found to have nodal disease on intraoperative frozen section. The previously biopsied/clipped node was confirmed as one of the SLNs in 9 (39.1 %) patients.
Fig. 3.
Axillary management amongst surgically node-positive axillae in adult women diagnosed with operable invasive breast cancer who received an ultrasound guided axillary core-needle biopsy with a negative result who then underwent upfront surgery at a single-institution from 2010 to 2020.
Key: pN+= node-positive on surgical pathology; SLNB = sentinel lymph node biopsy; ALND = axillary lymph node dissection.
4. Discussion
In this single-institution retrospective cohort study of women with invasive breast cancer and clinically and/or imaging suspicious axillary nodes with a negative US-CNBx who then underwent upfront surgery, the FNR of the US-CNBx in terms of detecting any axillary disease was found to be 24.4 % for all patients and 21.1 % for those with actionable axillary disease (excluding those with ITCs or micrometastasis only). Patients with pN + disease had larger tumors and findings suggest that a fewer number of CNBxs may be associated with an increased FNR. This study is unique in that the cohort is exclusive to patients undergoing US-CNBx and data representation from both academic and community sites, supporting a contemporary and generalizable FNR of axillary-node US-CNBx.
Our institution primarily uses US-CNBx for axillary nodal biopsies; however, there is variance in the use of US-CNBx vs US-FNA nationally. US-CNBx has been shown to have greater accuracy and specificity, as well as a lower FNR when compared with US-FNA.15,17–20 However, US-FNA remains an acceptable tool for nodal biopsies given that it is a low-risk procedure, has minimal complications, and has a reasonably acceptable rate of detecting axillary metastasis.17,18,21 Additionally, previous studies evaluating the efficacy of US-FNA and US-CNBx note the amount of tissue collected as a contributing factor to the differences between the two modalities,15,17 indicating that the more tissue sampled, the lower the FNR. Increasing the number of core biopsies taken increases the amount of tissue sampled thus improving the sensitivity and reducing the FNR as well.22 Our work may support this theory; though there was insufficient evidence, given that there was a greater mean number of core biopsies taken in the pN0 cohort compared to the pN + cohort.
In recent years, some centers have adopted an algorithm that all newly diagnosed breast cancer patients receive a formal axillary US to evaluate for occult nodal involvement.23 While this approach can support the decision for a NAC vs upfront surgery approach, it can also lead to overdiagnosis and potentially lead to surgical axillary overtreatment. Both the ACOSOG Z11 and EORTC AMAROS trials, which demonstrated that ALND can be spared in women cT1–T2 cN0 breast cancer who undergo upfront surgery and are found to have a low nodal burden, only required patients to have a normal clinical axillary exam.6,24 Thus, for those women who would have otherwise been Z11 and/or AMAROS eligible, routine axillary-US may lead to overdiagnosis and make them ineligible for surgical axillary de-escalation if found to have occult disease on CNBx. This is particularly notable for women with hormone-receptor positive disease in whom NAC or neoadjuvant endocrine therapy results in primary tumor downstaging, but much less often results in a complete nodal response.25–27 Further trials are needed to assess if patients with cN + hormone-receptor-positive disease who have an overall low nodal burden can forgo ALND in favor of SLNB, with or without a targeted axillary dissection. At our center, our team has adopted strategic measures after comprehensive multidisciplinary team discussion to selectively decide who undergoes axillary US despite having a normal clinical exam: those with a primary breast tumor ≥2 cm in size, those with multifocal or multicentric disease, or those with exam findings suggestive of inflammatory breast cancer. For patients with more aggressive tumor phenotypes, like TNBC, the timing of receipt of systemic chemotherapy does not change ALND rates in those who are cN0 and undergo upfront surgery28,29 – but routine axillary imaging, specifically for those with cT1c TNBC, may identify patients with occult nodal metastasis who are eligible for novel systemic therapies.8,30 Recent publication of the SOUND trial provides supportive evidence for the routine use of axillary-US in women with cT1 invasive breast cancer. In the SOUND trial, if axillary US was within normal limits and/or patients had a negative US-guided biopsy (fine needed aspiration), were randomized to SLNB or no axillary surgery at 5 years, there was no difference in axillary recurrence or distant metastasis between the two study arms.31
Nodal management in this cohort suggest adoption of surgical axillary de-escalation strategies in patients undergoing either breast conserving surgery or mastectomy as 73.7 % of patients with 1–2 positive nodes were spared ALND.32,33 Notably, our cohort spans a pre-Z11/AMAROS era and likely explains why some patients with a low nodal burden still received an ALND. Axillary nodal management trends from this data are consistent with recent national level data demonstrating increasing implementation of strategies to mitigate ALND in patients who are cN0 but found to be pN+ with an overall a low nodal burden of disease.34–36 In our cohort, of the 23 pN + axillary, two patients had ≥ pN1 HER2+ tumors and one had pN1 TNBC. These patients are notable given that if these patients were diagnosed in the current era and had their nodal disease been found on US-CNBx, they would have met criteria to receive pre-operative systemic therapy based on current guidelines.7–9 Thus, again demonstrating the role nodal disease plays in the timing and options for systemic chemotherapy in breast cancer patients.10
Artificial Intelligence (AI) has become a popular modality and holds promise in revolutionizing the radiological diagnosis of breast cancer.37,38 In 2021, a study found that when determining axillary nodal involvement of breast cancer patients, AI had a comparable performance to radiologists with an accuracy of 69.5 % 0.06 % compared to 70.1 % 0.07 % (p = 0.90), respectively, when predicting axillary nodal metastasis based upon US images.39 However, AI was shown to have less sensitivity but greater specificity.38 There have been additional studies supporting AI’s accuracy in detecting nodal involvement40,41 and AI holds promise in improving detection of breast cancer axillary nodal metastasis.
There are several limitations to this study. All patients received their care in the same geographic vicinity, within a single healthcare system and while this allowed for improved standardization of procedures and imaging interpretation, this restricts generalizability due to relatively homogenous patient demographics. Additionally, there is performance bias between individual physicians performing US, biopsies, and interpretation of imaging findings. We were not able to run a multivariable analysis given the limited significant findings on our univariable analysis. Furthermore, there are inherent limitations to our retrospective design such as missing data and charting practices not deliberately designed for data collection, such as lack of pathology documentation of confirmed presence of a biopsied and/or clipped node in many pathology reports and that specimen imaging was not performed to confirm removal of the clipped node in this cohort, likely given that the biopsied node was deemed benign via US-CNBx. Nevertheless, the strengths of this cohort include the system-wide standardization of practices and US-CNBx techniques and study design to include uniformity of patients who underwent CNBx only.
5. Conclusion
Women diagnosed with invasive breast cancer with clinically and/or imaging suspicious ipsilateral axillary nodes who have a negative US-CNBx and then underwent upfront surgery had an FNR of axillary guided US-CNBx of 24.2 % for all patients and 21.1 % for those with actionable axillary disease. Patients with pN + disease had larger tumors and our findings suggest that having a fewer number of CNBxs may be associated with an increased FNR. Thus, for patients who have a negative axillary US-CNBx with larger tumors, clinicians should have a higher level of suspicion for occult axillary disease and carefully consider the role of upfront surgery vs a NAC approach, particularly in those patients with HER2+ tumors or TNBC in whom systemic therapy treatments can be impacted by a NAC vs upfront surgery approach.
Funding
Cortina is supported by the National Institutes of Health (NIH) under Award Number 1K08CA276706–01A1 (PI: Cortina). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Footnotes
Declaration of competing interest
The authors have no relevant financial disclosures to report.
Ethics approval
This study was performed in line with principles of the Declaration of Helsinki. Approval was granted by the Institutional Review Board of the Medical College of Wisconsin.
Disclosures
The authors have no relevant financial disclosures to report.
CRediT authorship contribution statement
Christine Rogers: Writing – review & editing, Writing – original draft, Project administration, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Sarah Zeien: Writing – review & editing, Methodology, Investigation, Data curation, Conceptualization. Kaleen Puccetti: Methodology, Investigation, Data curation, Conceptualization. Julie M. Jorns: Writing – review & editing, Validation, Supervision, Methodology, Investigation, Data curation, Conceptualization. Amanda L. Kong: Writing – review & editing, Supervision, Investigation, Conceptualization. Solomon Cherian: Writing – review & editing, Supervision, Methodology, Investigation, Conceptualization. Chandler S. Cortina: Writing – review & editing, Writing – original draft, Supervision, Resources, Project administration, Methodology, Investigation, Formal analysis, Conceptualization.
Data availability
The dataset generated during the current study is not publicly available but is available upon reasonable request of the corresponding author.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The dataset generated during the current study is not publicly available but is available upon reasonable request of the corresponding author.