My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida.
I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016.
Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida.
Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.
SENOMAC enrolled some patients with ECE, cT3, and men
Prespecified subgroup analyses did not show detriment with ALND omission:
Though numbers are smaller – supporting wider generalizability makadu.live
After mastectomy with 1 to 2 positive SLNs, do I need ALND?
Not routinely – With planned comprehensive RNI, ALND can be omitted (AMAROS, SENOMAC) a position reflected in the 2025 ASTRO-ASCO-SSO PMRT guideline language emphasizing less invasive axillary management with nodal RT PubMed+2PubMed+2
Omission of any axillary surgery (SLNB-omission):
SOUND (JAMA Oncol 2023) – who can skip SLNB entirely?
Women with small tumors and negative axillary ultrasound:
Had noninferior 5-yr distant DFS with no axillary surgery vs SLNB
If axillary pathology doesn’t change therapy:
Omission is safe
INSEMA (NEJM 2024/2025) – does it reinforce SLNB omission?
Yes:
In cT1 to cT2 cN0 undergoing BCS + WBRT, omitting SLNB was noninferior for invasive DFS, with fewer arm morbidities:
Broadening omission beyond SOUND’s entry criteria
Guideline impact – what does ASCO 2025 now recommend?
ASCO now supports SLNB omission for select postmenopausal ≥50, HR+/HER2-, G1–2, ≤2 cm tumors with negative AUS undergoing BCS + RT, when nodal status won’t alter adjuvant therapy
How do I counsel a 65-year-old with 1.5 cm HR+/HER2–, AUS-negative tumor?
Discuss SLNB omission per ASCO 2025, referencing SOUND / INSEMA
Emphasize shared decision-making and document that nodal status won’t change systemic therapy / RNI plans
Does negative AUS define cN0 reliably enough to omit surgery?
In SOUND / INSEMA, AUS was adequate for selection:
Axillary failures were rare with omission when systemic / RT plans were appropriat:
Still, ensure imaging quality and consider biology.
Pathology definitions and “what counts”
Define ITCs vs micrometastases (AJCC 8e):
ITCs:
< 0.2 mm or < 200 cells (N0[i+])
Micrometastases:
0.2 mm to 2 mm (N1mi)
Management parallels the trials:
Micrometastases (IBCSG 23-01) often no ALND:
ITCs generally node-negative
Do ITCs change indications for ALND or RNI
ITCs typically do not mandate ALND:
Decisions on RNI hinge on comprehensive risk assessment rather than ITCs alone (Use institutional protocols)
Neoadjuvant chemotherapy (NAC): SLNB and TAD
ACOSOG Z1071 – what did we learn?
In biopsy-proven cN1→ycN0 after NAC:
SLNB had an FNR ≈ 12%:
Improved by dual tracer and retrieving ≥ 3 SLNs
Capturing the clipped node lowered the FNR further – ushering in targeted axillary dissection (TAD)
SENTINA – why was FNR a concern?
Complex 4-arm RCT showed higher FNRs when SLNB was performed after NAC in initially node-positive patients, especially when only 1 to 2 SLNs were retrieved:
Driving optimization:
Dual mapping, ≥ 3 SLNs and TAD
SN-FNAC (JCO 2015) – can SLNB be accurate post-NAC in cN+?
With mandatory IHC, ID rate 87.6% and FNR 8.4%:
When ≥ 2 SLNs were removed – evidence that optimized technique can make SLNB acceptable after NAC in prior cN+
GANEA-2 (2019) – safety signal?
Prospective multicenter study supported feasibility and safety of post-NAC SLNB with low axillary failure when using optimized protocols; informs modern post-NAC algorithms
What is TAD and why do it?
Targeted axillary dissection combines SLNB + removal of the pre-treatment clipped node:
To slash FNR vs SLNB alone and better mirror basin response – core idea from MD Anderson implementation work
RISAS / TAD accuracy – what’s the FNR
Multicenter diagnostic study of radioactive iodine seed localization (RISAS):
FNR 3.5%, NPV 92.8% – strong diagnostic performance for restaging after NAC
MARI protocol – how is it different?
Marking the positive node with a seed pre-NAC and excising it post-NAC; with PET-CT integration:
MARI can avoid ALND in ~80% of cN+ while keeping 3-yr axillary recurrence-free interval ~98%
TAD outcomes – can we safely omit ALND in responders?
Cohorts show low 3-yr axillary recurrence with TAD alone in good responders (and no survival decrement vs TAD + ALND in selected patients):
Remains one of the most powerful and actionable prognostic factors in oral tongue / oral cavity SCC
Classically, Scholl and colleagues:
Reviewed 268 patients with squamous carcinoma of the oral tongue:
They found that 54 (20.1%) had microscopic “cut-through” at the intraoperative frozen section margin:
An initially positive margin
Even when additional resection converted these to final negative margins:
Local control remained significantly worse:
Than in patients whose margins were clear on the first pass
They also reported that margin involvement patternsdiffered by T stage:
T1 to T2 tumors:
More often had positive mucosal margins
T3 to T4 tumors:
Commonly failed at the deep / soft-tissue margins
Similar observations were made in classic series evaluating “positive” epidermoid carcinoma margins in the head and neck:
Looser, Shah, and Strong:
Demonstrated that patients with involved margins:
Had substantially higher local recurrence than those with negative margins:
With early reports quoting local recurrence in roughly two-thirds to three-quarters of patients with positive margins versus about one-third with negative margins
Loree and Strong:
Subsequently examined 398 oral cavity SCCs:
Showing that positive or “close” margins (tumor at or within 0.5 mm of the inked edge, or significant premalignant change / in situ carcinoma at the margin):
Were associated with a doubling of local recurrence (36% vs 18%) and inferior 5-year survival compared with negative margins (52% vs 60%)
The reliability and utility of intraoperative frozen section (FS) margin assessment have also been extensively studied:
Spiro et al:
Reported an overall intraoperative FS diagnostic accuracy of approximately 89% for oral tongue cancer:
Importantly found that accuracy was similar whether sections were taken directly from the patient’s tumor bed or from the oriented surgical specimen
Positive or “close” margins:
Defined in their series as tumor present at the ink or within roughly one high-power field of the resection edge:
Were associated with a significantly increased risk of local recurrence (p < 0.003)
Subsequent work by Byers and others:
Confirmed the prognostic and therapeutic value of frozen section (FS):
Guided re-resection in HNSCC:
But also highlighted that FS cannot fully compensate for suboptimal initial resection planes
Definitions of margin status and distance:
There is now better consensus on margin nomenclature
Most contemporary series and guidelines define:
Positive margin:
Invasive carcinoma or severe / high-grade dysplasia:
At the inked edge, or < 1 mm from the inked edge
Close margin:
Invasive carcinoma typically 1 to 4 or 1 to 5 mm from the inked edge:
Cut-off values vary:
But a 5 mm microscopic threshold is most commonly used in oral cavity SCC
Clear margin:
≥ 5 mm from invasive tumor to the inked edge after formalin fixation
Tasche et al., in a large JAMA Otolaryngology analysis:
Proposed that a distance < 1 mm behaves biologically like an involved margin:
With similarly high local recurrence risk
Whereas 1 to 5 mm margins had intermediate risk and ≥ 5 mm margins were associated with the lowest recurrence
More recent multicenter work emphasizes the importance of deep margin distance in particular:
With data suggesting that deep margins ≤ 3 mm carry a significantly higher risk of local failure compared with > 3 mm:
Even when the mucosal margin is wide
Impact of positive and close margins on outcomes:
Multiple retrospective series and meta-analyses now support and refine the early observations of Scholl, Looser, Loree, and Strong:
Positive final margins are consistently associated with:
~ 2-fold higher risk of local recurrence, increased regional / distant failure in some series, and significantly worse disease-specific and overall survival
Binahmed et al. and McMahon et al:
Both showed that patients with involved margins:
Had roughly double the local recurrence and significantly poorer survival compared with those with clear margins, and that close margins behaved intermediately between clearly negative and frankly positive margins
Liao et al:
Identified margin status, together with T stage, DOI, and perineural invasion:
As major predictors of local tumor control in oral cavity SCC
A 2019 systematic review and meta-analysis by Gorphe:
Concluded that positive margins carry an approximately two-fold increased risk of death and local failure across head and neck sites, independent of other factors
More granular contemporary analyses, including Buchakjian et al. and Szewczyk et al., have shown that:
Close margins (1 to 4.9 mm) often do not independently worsen outcomes if other adverse factors (lymphovascular invasion, perineural invasion, ENE, nodal disease, advanced T stage):
Are absent and if appropriate adjuvant therapy is given when indicated
The prognostic effect of close margins is modulated by:
Depth of invasion, pattern of invasion, and composite histologic risk models (e.g., Brandwein-Gensler)
Subsite-specific studies have further refined this:
Tongue and floor-of-mouth tumors are particularly prone to failure at the deep margin:
In several series, deep margin positivity or ≤ 2 to 3 mm clearance:
Has been more predictive of local recurrence than mucosal margin distance
Microscopic cut-through and “revised” margins:
Building on Scholl’s original work, the concept of microscopic tumor cut-through (MTCT):
A positive FS margin that is revised to negative on final pathology, has been extensively studied
Patel et al. (Head & Neck 2010) showed that MTCT:
Was associated with significantly worse local control and disease-specific survival compared with margins that were negative from the outset:
Particularly in patients with nodal disease
Guillemaud et al. similarly reported that intraoperative cut-through, even if revised to R0:
Predicted higher local recurrence and worse outcomes in oral cavity SCC
A meta-analysis by Bulbul et al. concluded that clearance of a positive margin improves outcomes relative to leaving it unrevised:
But patients with MTCT still fare worse than those whose margins were always negative:
Suggesting MTCT is a marker of more aggressive biology and / or challenging local anatomy
More recently, Agne et al. evaluated T3 to T4 OCSCC and confirmed that MTCT:
remained an independent predictor of local recurrence on multivariable analysis (HR ~1.8–2.2 for local failure):
Although its effect on disease-specific survival attenuated when controlling for nodal stage and other high-risk features
These data support considering MTCT as a high-risk feature warranting discussion of treatment intensification:
For example (e.g., adjuvant chemoradiotherapy) in a multidisciplinary tumor board, even when final margins are technically negative
Kwok et al. addressed the related question of “clear versus revised margins” in 417 patients with oral and pharyngeal carcinoma:
Patients who required immediate re-resection for a positive FS margin but ended with R0 status:
Had survival similar to those with primary R0 resection, and both groups did substantially better than patients left with residual microscopic or macroscopic disease
This suggests that while MTCT carries biologic risk:
An aggressive intraoperative strategy to convert to R0 is still beneficial and should remain standard practice
Intraoperative margin assessment:
Specimen vs tumor bed:
There is growing recognition that how margins are sampled:
Is almost as important as the final measurement
Meier et al.’s AHNS survey and several subsequent series have documented wide variation in intraoperative margin practices (tumor bed vs specimen mapping, number of samples, definition of “adequate” clearance), and a substantial rate of FS–permanent section discrepancy
Key contemporary points include:
Specimen-based mapping (oriented and inked, with communication between surgeon and pathologist):
Tends to provide more reliable correlation between FS and final margins than random tumor-bed biopsies
FS accuracy remains high (often ~ 85% to 95%):
But false-negatives and false-positives still occur:
Particularly at the deep margin, in previously irradiated fields, and in specimens with significant shrinkage
In some series, “complete FS margins” with a measurable 1 to 5 mm histologic buffer were associated with improved local control compared with conventional limited sampling
Recent reviews and consensus statements (e.g., Kubik et al., Kain et al., Chen et al. 2024) now recommend:
A planned 1 to 1.5 cm gross resection margin in vivo for oral tongue SCC, anticipating ~30% to 50% shrinkage with formalin fixation and tissue relaxation
Routine use of oriented, inked specimens with targeted FS from high-risk areas (deep margin, close relationship to muscle bundles or neurovascular structures)
Consideration of advanced adjuncts—near-infrared fluorescence mapping, specimen 3D-mapping, and emerging augmented-reality registration—for difficult tongue and floor-of-mouth resections
Integration with histologic risk models:
Finally, margin status must be interpreted in the context of overall histologic risk
The Brandwein-Gensler model:
Worst pattern of invasion, perineural invasion, lymphocytic host response and later refinements:
Have shown that high-risk tumors have markedly increased recurrence and disease-specific mortality even when margins are clear
Conversely, some low-risk early-stage tumors with close (but not involved) margins may do well without aggressive adjuvant therapy
This supports a nuanced, risk-adapted approach in which:
Positive margins or MTCT → strong indication for adjuvant chemoradiotherapy in most patients
Close margins (1 to 4 mm) → individualized decision based on DOI, nodal status, PNI/LVI, pattern of invasion, and patient-specific factors
Clear margins (≥ 5 mm) → lowest risk group, managed according to other adverse features.
Reviewed:
Scholl P, Byers RM, Batsakis JG, Wolf P, Santini H. Microscopic cut-through of cancer in the surgical treatment of squamous carcinoma of the tongue: prognostic and therapeutic implications. Am J Surg. 1986;152:354-360.
Looser KG, Shah JP, Strong EW. The significance of “positive” margins in surgically resected epidermoid carcinomas. Head Neck Surg. 1978;1:107-111.
Loree TR, Strong EW. Significance of positive margins in oral cavity squamous carcinoma. Am J Surg. 1990;160:410-414.
Spiro RH, Guillamondegui O, Paulino AF, et al. Pattern of invasion and margin assessment in patients with oral tongue cancer. Head Neck. 1999;21:408-413.
Chen TY, Emrich LJ, Driscoll DL. The clinical significance of pathological findings in surgically resected margins of the primary tumor in head and neck carcinoma. Int J Radiat Oncol Biol Phys. 1987;13:833-837.
McMahon J, O’Brien CJ, Pathak I, et al. Influence of condition of surgical margins on local recurrence and disease-specific survival in oral and oropharyngeal cancer. Br J Oral Maxillofac Surg. 2003;41:224-231.
Binahmed A, Nason RW, Abdoh AA. The clinical significance of the positive surgical margin in oral cancer. Oral Oncol. 2007;43:780-784.
Liao CT, Chang JTC, Wang HM, et al. Analysis of risk factors of predictive local tumor control in oral cavity cancer. Ann Surg Oncol. 2008;15:915-922.
Patel RS, Goldstein DP, Guillemaud J, et al. Impact of positive frozen section microscopic tumor cut-through revised to negative on oral carcinoma control and survival rates. Head Neck. 2010;32:1444-1451.
Guillemaud J, Patel RS, Goldstein DP, et al. Prognostic impact of intraoperative microscopic cut-through on frozen section in oral cavity squamous cell carcinoma. J Otolaryngol Head Neck Surg. 2010;39:370-377.
Kwok P, Gleich O, Hübner G, Strutz J. Prognostic importance of “clear versus revised margins” in oral and pharyngeal cancer. Head Neck. 2010;32:1479-1484.
Gorphe P. A systematic review and meta-analysis of margins in head and neck cancer. Oral Oncol. 2019;95:93-101.
Tasche KK, Buchakjian MR, Pagedar NA, Sperry SM. Definition of “close margin” in oral cancer surgery and association of margin distance with local recurrence rate. JAMA Otolaryngol Head Neck Surg. 2017;143:1166-1172.
Buchakjian MR, Tasche KK, Robinson RA, et al. Association of main specimen and tumor bed margin status with local recurrence and survival in oral cancer surgery. JAMA Otolaryngol Head Neck Surg. 2016;142:1191-1198.
Kain JJ, Birkeland AC, Udayakumar N, et al. Surgical margins in oral cavity squamous cell carcinoma: current practices and future directions. Laryngoscope. 2020;130:128-138. Szewczyk M, et al. A matter of margins in oral cancer—how close is enough? Cancers (Basel). 2024;16(8):1488.
Agne GR, et al. Oncologic outcomes of microscopic tumor cut-through in locally advanced oral squamous cell carcinoma. Arch Head Neck Surg. 2022;51:e20220013. Chen Y, et al. Surgical margins in head and neck squamous cell carcinoma. Int J Surg. 2024;109:54-66.
Brandwein-Gensler M, et al. Oral squamous cell carcinoma: histologic risk assessment, but not margin status, is strongly predictive of local disease-free and overall survival. Am J Surg Pathol. 2005;29:167-178.
The treatment landscape for HER2-positive early breast cancer (EBC) is evolving rapidly — and trastuzumab deruxtecan (T-DXd) is emerging as a potential new standard in both the neoadjuvant and adjuvant settings.
🔹 Neoadjuvant Setting
DESTINY-Breast11
T-DXd followed by THP (docetaxel + trastuzumab + pertuzumab) demonstrated:
Significantly higher pathologic complete response (pCR) rates compared with standard anthracycline-based regimens A chemotherapy-sparing strategy with reduced anthracycline exposure Favorable tolerability profile consistent with prior T-DXd data
📊 Early reports show pCR rates approaching ~65–70%, exceeding historical benchmarks for standard neoadjuvant regimens (typically ~55–60%).
Clinical Implication:
We may be entering an era of antibody–drug conjugate (ADC)-based neoadjuvant intensification, potentially redefining the backbone of HER2-directed therapy.
Reference:
Hurvitz SA et al. DESTINY-Breast11. Presented at ESMO 2024 / SABCS 2024 (late-breaking data).
🔹 Adjuvant Setting
DESTINY-Breast05
For patients with residual invasive disease after neoadjuvant therapy, T-DXd demonstrated:
53% reduction in risk of invasive disease–free survival (iDFS) events compared with T-DM1 Superior invasive disease–free survival Manageable toxicity, with ILD rates consistent with prior experience
This builds upon the paradigm established by KATHERINE, where T-DM1 replaced trastuzumab in patients with residual disease.
Now, T-DXd appears poised to replace T-DM1 in this high-risk population.
Reference:
DESTINY-Breast05. Presented at ASCO 2025.
von Minckwitz G et al. KATHERINE trial. NEJM. 2019;380:617–628.
🔬 Why This Matters
We are witnessing:
A shift from monoclonal antibodies → ADC-based escalation Earlier deployment of highly potent HER2-directed agents Refinement of risk-adapted therapy based on response
If adopted into guidelines (NCCN, ASCO, ESMO), this could:
Redefine the management of residual disease Potentially reduce recurrence risk further in high-risk HER2+ EBC Change neoadjuvant sequencing strategies
⚠️ Considerations
ILD/pneumonitis risk requires vigilance Cost-effectiveness and long-term survival data pending Optimal sequencing with pertuzumab still being clarified
📌 Bottom Line
T-DXd is no longer just a metastatic drug.
It is rapidly reshaping the curative-intent HER2+ early breast cancer algorithm.
Choledochal cysts are congenital cystic dilatations of the biliary tree. They are associated with an abnormal pancreaticobiliary junction and carry a significant lifetime risk of malignancy (especially cholangiocarcinoma).
Classification (Todani Classification)
The most widely used system is the Todani classification, which divides choledochal cysts into five main types:
Type I – Extrahepatic bile duct dilatation (most common, 50–80%) • Ia – Diffuse cystic dilatation of CBD • Ib – Focal segmental dilatation • Ic – Fusiform dilatation of CBD
Management: → Complete excision of extrahepatic bile duct + Roux-en-Y hepaticojejunostomy
Type II – True diverticulum of CBD • Saccular outpouching from extrahepatic bile duct
Management: → Diverticulectomy ± primary closure of CBD
Type III – Choledochocele • Intraduodenal dilatation of distal CBD (within ampulla)
Type IV – Multiple cysts • IVa – Both intrahepatic and extrahepatic involvement • IVb – Multiple extrahepatic cysts only
Management: → Excision of extrahepatic bile duct + Roux-en-Y hepaticojejunostomy → Liver resection if localized intrahepatic disease → Liver transplant if diffuse severe intrahepatic disease
Type V – Caroli Disease • Multiple intrahepatic cystic dilatations only
Mirizzi Syndrome: The rare but challenging complication where an impacted gallstone in the cystic duct or Hartmann’s pouch causes external compression or fistulization into the common bile duct. The modified Csendes classification grades severity from Type 1 (external compression only) through Type 5 (cholecystobiliary fistula with gallstone ileus). Type 1 shows simple compression without fistula formation. Type 2 involves erosion affecting less than one-third of the bile duct circumference. Type 3 extends to involve one-third to two-thirds of the duct. Type 4 shows complete destruction of the bile duct wall. Type 5 adds the complication of cholecystoenteric fistula with gallstone ileus. Recognition is critical during cholecystectomy as misidentification can lead to bile duct injury. Higher types require bile duct reconstruction
New 5-Year Evidence Supporting Radiofrequency Ablation (RFA) in Early-Stage Breast Cancer
I’m pleased to share results from the RAFAELO Phase 3 multicenter trial — published online in Annals of Surgical Oncology (Feb 18, 2026) — assessing radiofrequency ablation (RFA) as a minimally invasive alternative to partial mastectomy in early-stage breast cancer.
• Population: 370 women with solitary Tis–T1 (≤1.5 cm), N0M0 breast carcinomas.
• Intervention: Percutaneous RFA followed by whole-breast radiation (45–60 Gy).
• Primary Endpoint: 5-year ipsilateral breast tumor recurrence-free survival (IBTRFS).
📈 Key Findings
✔ At 5 years, IBTRFS was 98.6% (90% CI 97.1–99.3%), exceeding the pre-specified noninferiority margin of 90%.
✔ Only 2 ipsilateral recurrences were observed at 5 years.
✔ Grade ≥3 skin ulceration was rare (1/370 patients), underscoring a favorable safety profile.
✔ These results suggest that RFA with adjuvant radiation may be comparable to partial mastectomy in appropriately selected early-stage patients.
🏷 Clinical Significance
This large prospective trial provides the most robust long-term evidence to date that RFA — a less invasive approach — may be a viable local-control strategy in small, node-negative breast cancers. These findings reinforce ongoing interest in expanding treatment options that balance oncologic safety with patient-centred care (e.g., cosmesis, procedural morbidity).
Optional Add-Ons for Engagement
🔹 Thanks to the RAFAELO Study Group and contributing centers for advancing patient-centred oncology.
🔹 Looking forward to longer follow-up, quality-of-life data, and comparative trials against standard surgery
Conference Overview Held March 12–15, 2025 in Vienna with >3,100 global participants. Focused on early breast cancer (BC): evidence, controversies, consensus, and breakthroughs. Included lectures, debates, poster sessions, and the renowned St. Gallen Consensus Session. Hansjoerg Senn Memorial Lecture was introduced to honor a major contributor to BC care.
🔬 Systemic Therapy & Novel Agents Goal of early BC therapy is to improve overall survival (OS) through better systemic and local treatment. Surrogate endpoints (e.g., pathological complete response) are crucial for accelerating drug development. New endocrine therapies (SERDs) are being evaluated, with emphasis on QoL and resistance mechanisms. Anti-HER2 advances from metastatic setting are being translated to early BC, including adaptive trial designs. Antibody-drug conjugates (ADCs) hold potential in early BC; ongoing trials are evaluating various indications.
🧬 Liquid Biopsy & Biomarkers ctDNA and liquid biopsy show promise for minimal residual disease (MRD) detection and relapse risk stratification. Tumor-informed assays have higher sensitivity than tumor-agnostic panels. Circulating tumor cells (CTCs) are prognostic but less sensitive; CHIP mutations may confound results. Multiple trials are exploring ctDNA as a tool for guiding post-treatment strategies.
HER2+ Breast Cancer Trastuzumab remains a foundational therapy after 20 years. Duration of trastuzumab (6 vs. 12 months) continues to be debated; 12 months remains standard. Improved HER2 testing and classification helps tailor therapies, especially in HER2-low disease. De-escalation strategies (e.g., PET-adapted) are under study for selected patients. Residual disease post-neoadjuvant therapy moves toward T-DM1 or other combinations; new trials are ongoing.
Tailoring Treatment & De-Escalation Omitting radiotherapy (RT) or endocrine therapy (ET) in very low-risk patients is under investigation. Minimally invasive alternatives (e.g., cryoablation) are being evaluated to reduce surgical burden. Older patients need individualized decision making rather than age-based exclusion from therapy. Tools like ESMO Magnitude of Clinical Benefit Scale can help weigh benefits vs toxicity.
Surgery & Local Management Breast-conserving surgery (BCS) remains preferred when feasible; mastectomy does not guarantee survival benefit. Radiotherapy tailoring (partial, hypofractionation) reduces toxicity while maintaining control. Post-neoadjuvant surgery focuses on resection of residual disease; MRI radiomics and biopsies aid prediction. Reconstruction decisions must be individualized, involving patient preferences and RT considerations.
ER+ Disease Nuances Optimizing adjuvant therapy (ET, CDK4/6 inhibitors, genomic assays) depends on recurrence risk and biomarkers. Chemotherapy benefit varies by genomic risk scores and age—particularly in premenopausal women. Extended ET decisions benefit from clinical, genomic, and novel biomarkers like ctDNA. Invasive lobular carcinoma (ILC) and ER-low tumors need refined imaging and therapeutic stratification.
Artificial Intelligence (AI) Integration AI has potential to enhance: Biomarker discovery and response prediction Treatment planning and radiation delivery Target identification and clinical decision support Collaboration between AI developers and clinicians is essential for clinical implementation.
Imaging & Staging Updates PET-CT may be useful in higher-stage early BC; routine use in stage I remains limited. Breast MRI improves staging but increases interventions without clear outcome benefit; selective use recommended. Follow-up imaging remains guided by existing evidence; future strategies might integrate new technologies and ctDNA.
Hereditary BC & Prevention Germline mutations (BRCA1/2, PALB2, ATM, CHEK2) justify altered management and intensive screening. Risk-reducing surgeries lower incidence, though survival benefits require longer follow-up. Non-surgical options (e.g., intensified screening, risk-reducing medications) are important for many carriers.
Axillary Management Sentinel lymph node biopsy (SLNB) remains standard for clinically node-negative patients. Omission of upfront axillary surgery is considered in select scenarios with multidisciplinary input. Trials are evaluating safe approaches to avoid full axillary dissection post-neoadjuvant therapy.
Clinical Trials & Patient-Centered Design High-quality trials require real-world applicability, patient involvement, meaningful endpoints, and QoL measures. Trial design frameworks (e.g., SPIRIT, PRECIS-2) help balance explanatory vs pragmatic objectives.
Special Populations BC during pregnancy requires tailored imaging and therapy planning to optimize maternal and fetal safety. Young patients and those with reproductive concerns need individualized counseling and treatment adaptation.
Rodrigo Arrangoiz MS, MD, FACS, FSSO 