Breast cancer is the most commonly diagnosed cancer in the world, with a higher incidence in developed countries. Early diagnosis rates are high, ensuring that numerous small tumors are surgically treatable [14, 15].

Currently, the trend is to have entered a phase of de-escalation in treatment. In our study, cryoablation effectively eradicated 97% of pure IDC and 82% of mixed IDC cases. Among the variables examined, both DCIS and tumor size show significant positive correlation with RIC (p = 0.09, 95% CI). Positive DCIS significantly increases the likelihood of finding Residual Invasive Cancer within the surgical specimen post-cryoablation, with an OR of 7.43. Similarly, with every unit increase (mm) in tumor Size, the OR for RIC increases 1.2. These findings are in concordance with those published by Poplack et al. [16].

The presence of DCIS nests away from the cryoablation focus do not impact patient management or prognosis, given that all lumpectomy specimens had clear surgical margins.

Studies have shown that unifocal T1-T2 tumors may show subclinical invasive carcinoma foci or DCIS foci remote to the primary tumor. Holland published an examination of mastectomy specimens from patients diagnosed with IDC, revealing that 20% of invasive T1-T2 cancers had foci within 2cm of the primary tumor, and 43% extended beyond this boundary [17].

In 2013 a consensus document elaborated by a multidisciplinary expert panel was released, indicating that if an infiltrating cancer is completely surgically removed (tumor-free margins confirmed by pathology), there is no increased relapse risk if patients complete subsequent adjuvant treatments like radiotherapy (RT) and endocrine therapy [2, 18]. Outside cryoablation areas, DCIS nests will likely disappear after adjuvant RT [19].

Clinicopathologic feature analysis between IDC and IDC/DCIS patients reveals that mixed tumors display over 50% multifocality compared to pure tumors. Additionally, FDG PET analysis suggests that unifocal IDC/DCIS tumors may present with undetected radiological multifocality [20].

The impact of various factors on the elevated re-excision rate following breast-conserving surgery (BCS) has also been examined. A study emphasized the crucial role of coexisting DCIS in producing positive margins, as delineating these tumors may be challenging [21]. Accurate estimation is vital for cryoprobe selection. Substantial underestimation by US is recognized in invasive lobular carcinoma (ILC) and IDC/DCIS [22, 23]. Some argue that MRI is the best predictor for tumor size, especially for mixed tumors. The presence of DCIS reduces lesion visibility and margin definition [24, 25]. Thus, for mixed infiltrating tumors, the ice ball generated during cryoablation should widely encompass the tumor size estimated by both ultrasound and MRI.

While acknowledging that 60 cases may not constitute a large sample, in cases 9 and 14 in our series RIC was present in the surgical specimen, and both were IDC/DCIS tumors of 10 and 12 mm treated with IceSphere needles. Following these cases, we opted to choose probes that would allow for the formation of larger ice balls. In the subsequent 3 patients with mixed tumors measuring 10 and 12 mm treated with 14G IcePearl probes, the technique was successful.

Ideally, as depicted by the needle manufacturer, completely encasing the tumor with a 5-10 mm margin in its major diameter is optimal. At 0 °C, the ice is visible but may not be lethal. Lethal temperatures are reached at -20° and −40 °C. A larger tumor, of up to 12 mm, may be encased with sufficient 5 mm margins using an IceSphere needle, as it may achieve a lethal area of approximately 22 mm × 28 mm.

However, when dealing with IDC/DCIS tumors, where establishing tumor margins and size can be more challenging, using an IcePearl needle will increase the likelihood of treatment success as we can ensure a maximum lethal zone of 27 mm × 32 mm.

Based on our experience, a 17G cryoprobe is suitable for tumors ≤ 12 mm without DCIS in the CNB and ≤ 10 mm if the tumor shows an intraductal component.

In 2004, Sabel et al. [26] reported a 100% success rate with argon cryoablation for tumors under 1cm and 82% for those under 2 cm, after studying 27 tumor samples.

In two studies on breast tumor cryoablation published in 2015 and 2016, success rates of 92–95% were reported if DCIS nests away from the ablated area were not considered as failures [16, 22].

Our findings align with the data published by Poplack et al. [16] who found instances of residual infiltrating components in tumors with non-calcified DCIS alongside IDC. Similarly, our pathologists described millimetric RIC foci in the periphery of the specimens, not at the cryoablation bed center. We believe the technique becomes ineffective when tumors surpass ice ball dimensions. Figure 6 (a-d) Macroscopic and microscopic images of the surgical specimen.

Macroscopic and microscopic images of the surgical specimen with 14G seed after cryoablation of a 12 mm HR + Her2- Ki 67:10 Luminal A IDC/DCIS tumor. (a) Radiographic representation of the surgical specimen revealing the coexistence of the tumor, the seed, and a peripheral region displaying post-cryoablation fat necrosis (indicated by blue arrows). (b) Macroscopic view of the specimen marked with ink. (c) One of the serial fillets through the center of the hemorrhagic necrosis * with (Sirius) seed. (d) Two-millimeter foci of Residual Invasive Cancer (RIC) distant from the region of fat necrosis marked by the dashed line and in proximity to the specimen’s periphery, maintaining separation from the inked margin. ypT1aN0Mx. Note: IDC Infiltrating ductal carcinoma, DCIS Ductal carcinoma in situ, RIC Residual invasive cancer

Six patients reported mild discomfort that did not warrant intervention, and only one experienced moderate to severe pain that responded well to standard oral analgesia and anti-inflammatory medication. Only one patient presented with a small (5 mm) skin vesicle.

Four out of the 5 cases where RIC foci remained post-procedure were associated with tumors containing DCIS. Both variables, DCIS and tumor size, were significantly associated with technique failure (p = 0.09).

This outcome is consistent with expectations, as tumors coexisting with DCIS are known to display greater multifocality that may not be detectable by imaging.

At our facility, MRI is used to stage luminal tumors under 2 cm that show an intraductal component in the CNB, which is not apparent from microcalcifications on mammography.

Among 22 patients with mixed IDC/DCIS, 4 declined MRI. Subsequent specimen assessment revealed RIC in 2 of these cases (50%). Thus, there is a possibility that tumor size was underestimated in these cases.

The first case of technique failure involved a mixed tumor where the participant declined MRI staging. The tumor was initially assessed ultrasonographically at 12 mm. However, an X-ray of the surgical specimen revealed spicules with pathological microcalcifications extending up to a 2 cm diameter. Additionally, the pathologist described an indurated tumor within the specimen, with a maximum diameter of 16 mm. This patient was number 12 in our series, and due to our limited experience at that time, we chose a 17G needle which was not appropriate for the actual size of the tumor.

In the only case with a 16 mm pure IDC that showed post-ablation RIC, a 17G probe was used due to the unavailability of a 14G needle, leading to insufficient ice coverage of the tumor.

The conclusion derived from our study is that the technique becomes ineffective when the tumor exceeds the size of the surrounding ice area. It is crucial to make the most accurate estimation possible of tumor size, relying on all available imaging methods.

Efficacy is related to the chosen ice ball diameters, proper probe placement, and the exact tumor size.

Our study had some limitations, including being single institution, a potentially insufficient sample size and the lack of universal MRI staging.

Pending the results of studies like ICE3 and others, coupled with advancements in axillary surgery de-escalation like the omission of SLNB based on the conclusions of the St Gallen 2023 SOUND study, cryoablation could emerge as a viable treatment option for pure IDC ≤ 2 cm [13, 27,28,29].

With consensus from a multidisciplinary medical board, physicians with experience in breast pathology are key in the selection, procedure execution and follow up of these patients.