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• Chemoprevention:
  • With a selective estrogen receptor modulator:
    • Such as tamoxifen:
      • Substantially reduces the risk of developing invasive breast cancer in patients with lobular carcinoma in situ (LCIS) and should be offered
• Negative margins are generally not required for classic LCIS:
  • Whereas they are recommended for:
    • Pleomorphic LCIS
• The patient’s future risk of developing breast cancer is:
  • Approximately 1% annually
• Bilateral prophylactic mastectomy:
  • Is generally considered to be more invasive than is required in this setting and, although it could be discussed as an option, should not be routinely recommended
• References:
  • Page DL, Kidd TE Jr, Dupont WD, Simpson JF, Rogers LW. Lobular neoplasia of the breast: higher risk for subsequent invasive cancer predicted by more extensive disease. Hum Pathol. 1991;22(12):1232-1239.
  • Andersen JA. Lobular carcinoma in situ of the breast. An approach to rational treatment. Cancer. 1977;39(6):2597-2602.
  • Akashi-Tanaka S, Fukutomi T, Nanasawa T, Matsuo K, Hasegawa T, Tsuda H. Treatment of noninvasive carcinoma: fifteen-year results at the National Cancer Center Hospital in Tokyo. Breast Cancer. 2000;7(4):341-344.
  • Walt AJ, Simon M, Swanson GM. The continuing dilemma of lobular carcinoma in situ. Arch Surg. 1992;127(8):904-907.
  • Haagensen CD, Bodian C, Haagensen DE. Neoplasia (lobular carcinoma in situ). In Breast Carcinoma: Risk and Detection. Philadelphia, PA: WB Saunders, 1981.
  • Wong SM, King T, Boileau JF, Barry WT, Golshan M. Population-based analysis of breast cancer incidence and survival outcomes in women diagnosed with lobular carcinoma in situ. Ann Surg Oncol. 2017;24(9):2509-2517.
  • Fisher ER, Land SR, Fisher B, Mamounas E, Gilarski L, Wolmark N. Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: twelve-year observations concerning lobular carcinoma in situ. Cancer. 2004;100(2):238-234.

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• DCIS is generally classified as one of five subtypes:
  • Based on differences in the architectural pattern of the cancer cells and nuclear features:
    • Comedo
    • Solid
    • Cribriform
    • Micropapillary
    • Papillary
  • Cribriform, comedo, and micropapillary:
    • Are the most common subtypes:
      • Although two or more patterns coexist:
        • In up to 50% of cases
• The classification of noninvasive breast cancer:
  • Stratifies lesions based on their:
    • Likelihood of recurrence and incorporates prognostic factors
• Lagios et al. (1989):
  • Identified high nuclear grade and comedonecrosis:
    • As factors predictive of local recurrence
  • Patients whose tumors had a high nuclear grade and comedonecrosis:
    • Had a 19% local recurrence rate after lumpectomy alone at an average interval of 26 months:
      • Compared with 5% for those patients:
        • Whose tumors did not have necrosis and were a lower nuclear grade
• Silverstein et al. (1995):
  • Developed the Van Nuys algorithm:
    • To stratify patients into three risk groups using three established predictors of local recurrence:
      • Tumor size
      • Margin width
      • Pathologic classification:
        • The presence or absence of comedonecrosis and / or high tumor grade
    • Now updated to include:
      • Age
• The University of Southern California / Van Nuys Prognostic Index Scoring System:
  • Can be used to determine which patients with DCIS are at greatest risk for recurrence:
    • And would therefore benefit from particular forms of locoregional therapy
  • With the goal being a local recurrence rate:
    • Of less than 20% at 12 years
  • Surgical excision alone:
    • Is recommended for a patient with a:
      • Score of 4 to 6
      • Score of 7:
        • But have margins ≥ 3 mm
  • Excision plus radiation therapy:
    • Is recommended for patients with a:
      • Score of 7 and margins < 3 mm
      • Score of 8 and margins ≥ 3 mm
      • Score of 9 and margins ≥ 5 mm
  • Mastectomy:
    • Is recommended for a:
      • Score of 8 and margins < 3 mm
      • Score of 9 and margins < 5 mm
      • Score of 10 to 12
  • The USC/VNPI score may be a useful adjunct in therapeutic decision making:
    • But multiple attempts at independently validating the utility of this risk stratification scheme have not been consistent
• Currently, there is no universally accepted classification system for DCIS

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• Ductal carcinoma in situ (DCIS):
  • Is a noninvasive carcinoma of the breast
  • It is defined as the proliferation of malignant epithelial cells:
    • Confined to the mammary ducts and without evidence of invasion through the basement membrane
  • Because it is noninvasive:
    • DCIS does not pose a risk of metastasis
• Lobular carcinoma in situ (LCIS):
  • Was previously considered a form of noninvasive carcinoma:
    • But is now understood to be a benign entity that is a pathologic marker of increased breast cancer risk:
      • In either breast
  • Atypical lobular hyperplasia (ALH) and LCIS:
    • Are both forms of lobular neoplasia and, together with atypical ductal hyperplasia (ADH):
      • Represent proliferative nonmalignant breast lesions

• Ductal carcinoma in situ (DCIS):
  • Is, by definition, a non-invasive breast malignancy confined to the ductal system:
    • But in a meaningful minority of cases, pathologists identify a tiny focus of invasion measuring 1 mm or less—so-called DCIS with microinvasion (DCISM)
  • How often does this actually happen?
    • The answer depends on how you frame the question.
• The Short Answer:
  • Microinvasion is identified in roughly:
    • 5% to 10% of all DCIS cases
  • DCIS with microinvasion:
    • Accounts for about 1% to 2% of all breast cancers (Sopik et al., Breast Cancer Research and Treatment, 2018; Zheng et al., Journal of International Medical Research, 2020)
• The reported rate varies widely, however, and two very different clinical questions often get lumped together:
  • What proportion of diagnosed DCIS turns out to contain a microinvasive focus?
  • How often does a core-biopsy diagnosis of DCIS get upstaged at surgical excision?
• Microinvasion Within Diagnosed DCIS:
  • In large surgical and pathologic series:
    • The numbers cluster at the lower end of the 5% to 10% range:
      • The UK Sloane Project (n = 11,285) recorded microinvasion in 4.6% of DCIS patients:
        • Though individual screening units reported rates anywhere from 0% to 25% (Shaaban et al., British Journal of Cancer, 2022)
      • A single-center series of 148 surgically treated DCIS cases:
        • Found microinvasive foci in 14.9% (Scheidegger et al., Human Pathology, 2025)
      • The spread largely reflects differences in how aggressively specimens are sectioned and sampled

• Upstaging From Core Biopsy:
  • Because core-needle biopsy samples only a fraction of the lesion:
    • DCIS diagnosed on core biopsy is frequently “upstaged” once the whole specimen is examined:
      • Approximately 6.6% of core-biopsy DCIS is upstaged to microinvasive disease, and around 22% to frank invasive carcinoma:
        • With an overall upstaging range of 8% to 47% across studies (Walters et al., Histopathology, 2015).
  • A meta-analysis cited by the American College of Radiology:
    • Reported an overall DCIS-to-invasive upstaging rate of 25.9% (Kuzmiak et al., Journal of the American College of Radiology, 2025)
  • When the core biopsy already shows microinvasion:
    • Upstaging to measurable invasive cancer (> 1 mm) occurs in about 28% to 37%:
      • Yet nodal positivity remains low (~1% to 7%) (Phantana-Angkool et al., Annals of Surgical Oncology, 2019)
• What Predicts Microinvasion?
  • Microinvasion is consistently linked to:
    • Higher-risk DCIS features
  • Independent predictors in the Sloane Project and other series include:
    • High nuclear grade
    • Large DCIS extent (≥ 2.6 cm)
    • Comedo necrosis
    • Solid / cribriform architecture
    • PR negativity (Shaaban et al., British Journal of Cancer, 2022; de Mascarel et al., Cancer, 2002)
• Why It Matters Clinically:
  • Despite the “invasive” label, microinvasive disease carries a low nodal metastasis rate (roughly 2% to 6%, range 0% to 20%) and a generally favorable prognosis (Sopik et al., Breast Cancer Research and Treatment, 2018):
    • For this reason, management largely follows DCIS principles:
      • Including the DCIS margin standard of > 2 mm
  • That said, the Sloane Project offered an important caveat:
    • Compared with pure DCIS, microinvasive disease was associated with:
      • Higher distant metastasis (1.2% vs 0.3%) and higher breast cancer mortality (2.1% vs 0.8%):
        • Suggesting more aggressive biology in a subset of patients (Shaaban et al., British Journal of Cancer, 2022)
• The Takeaway for Readers:
  • “Incidence of microinvasion in DCIS” is best answered with a range—about 5% to 10% of diagnosed DCIS:
    • Nearer 5% in rigorously standardized series, while keeping the separate upstaging question in mind when counseling patients after a core-biopsy diagnosis

• Multifocal DCIS is generally defined as:
  • DCIS present as two or more foci separated by at least 5 mm within the same breast quadrant
• Most investigators believe that multifocal disease:
  • In fact represents intraductal spread from a single focus of DCIS
• By careful serial subsectioning, Holland et al. (1990):
  • Demonstrated that multifocal lesions that appeared to be separate using traditional pathologic techniques:
    • Actually originated from the same focus in 81 of 82 mastectomy specimens

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• Multicentric DCIS is defined as:
  • DCIS presenting as separate, discontinuous foci of disease involving more than one quadrant
• The reported incidence of multicentricity may depend on the extent of the pathologic review and therefore varies:
  • From 18% to 60%
• Because mammary lobules are not constrained by artificially imposed quadrant segregations:
  • Cursory pathologic examination:
    • May incorrectly interpret contiguous intraductal spread as multicentricity
• Approximately 96% of all local recurrences:
  • After treatment of DCIS occur in the same quadrant as the index lesion:
    • Implicating residual untreated disease:
      • Rather than multicentricity as the cause of recurrence

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• Oropharyngeal tumor histological types:
  • Squamous cell carcinoma (SCC):
    • Is the most common malignancy of the oropharynx:
      • Making up 90% of the tumors in this region
  • Non-Hodgkin’s lymphomas:
    • Accounts for 8% of tumors in these region
  • Minor salivary gland tumors:
    • Account for 2% of tumors in these region
• With regard to squamous cell carcinoma:
  • The most frequent locations of affected sites is:
    • Tonsil / lateral wall:
      • 60% of the cases
    • Tongue base:
      • 25% of the cases
    • Soft palate:
      • 10% of the cases
    • Posterior pharyngeal wall:
      • 5% of the cases

• The eighth edition of the American Joint Committee on Cancer (AJCC) staging system:
  • Defines microinvasion as:
    • Invasion of breast cancer cells:
      • Through the basement membrane at one or more foci:
        • None of which exceeds a dimension of 1 mm
  • DCIS:
    • Is a Tis lesion:
      • Is classified as stage 0 cancer
  • DCIS with microinvasion is considered:
    • T1mi:
      • Upstages DCIS from stage 0 to stage I disease:
        • The earliest stage of invasive cancer:
          • In the AJCC staging system
• By definition:
  • DCIS does not have the ability to metastasize to axillary lymph nodes or distant sites:
    • Whereas DCIS with microinvasion does
• Axillary metastasis:
  • Has been reported in 0% to 20% (0% to 28% in some series) of patients:
    • With DCIS with microinvasion
• The incidence of microinvasion in DCIS:
  • Varies according to:
    • The size and extent of the index lesion
  • Lagios et al. (1989):
    • Reported a 2% incidence of microinvasion in patients with DCIS:
      • Measuring ≤ 25 mm in diameter
    • Compared with a 29% incidence of microinvasion:
      • In those with lesions ≥ than 26 mm
  • The incidence of microinvasion is also higher in patients with:
    • High-grade or comedo-type DCIS with necrosis
    • In patients with DCIS who present with:
      • A palpable mass
      • Nipple discharge
• Historically, patients with DCIS with microinvasion:
  • Have been observed to have a worse prognosis:
    • Compared with those who have DCIS alone
  • Mirza et al. (2000):
    • Reported the long-term results of breast-conserving therapy in patients with:
      • DCIS
      • DCIS with micro-invasion (T1mi)
      • T1 invasive breast cancers
    • The 20-year disease-specific survival rates in patients with:
      • DCIS were better:
        • Than those among patients with DCIS with microinvasion or with T1 invasive tumors
      • Patients with micro-invasion (T1mi) and those with T1 tumors:
        • Had similar survival rates
  • In a retrospective study of 1,248 serially sectioned DCIS tumors, de Mascarel et al. (2002):
    • Reported a 10.1% incidence of axillary metastases:
      • In cases of DCIS with microinvasion
    • Patients with DCIS had a better 10-year distant metastasis-free survival rate:
      • Than patients with DCIS with microinvasion:
        • 98% and 91%, respectively
    • The overall survival rate was also better in patients with DCIS compared to DCIS with microinvasion:
      • 96.5% vs. 88.4%
    • However, the metastasis-free and overall survival rates:
      • Were worse in patients with invasive ductal carcinoma compared with those with DCIS with microinvasion
    • These results suggest that DCIS with microinvasion:
      • Should be characterized as a small invasive tumor with a good outcome:
        • The therapeutic approach for these patients should be similar to that for patients with invasive cancer
• However, more recent studies have pointed toward DCIS with microinvasion having a more similar natural history to pure DCIS than to early-stage invasive disease:
  • In a review of 393 patients treated at Yale between 1973 and 2004:
    • There was no statistically significant difference between patients with DCIS and those with DCIS with microinvasion with regard to the presence of axillary metastases (in those who had axillary staging) or the likelihood of recurrence (locoregional and distant) or overall survival (Parikh et al., 2012)

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• Lobular neoplasia:
  • Is an atypical proliferation of small, dyscohesive epithelial cells:
    • Within the terminal duct lobular unit (TDLU):
      • That encompasses both:
        • Atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS)
• The hallmark feature is:
  • Loss of E-cadherin expression:
    • Resulting in cellular discohesion
• Lobular neoplasia:
  • Functions as both a:
    • Risk factor and non-obligate precursor to invasive breast carcinoma:
      • With LCIS conferring a 7-to-10-fold increased risk of breast cancer compared to the general population
• Definition and Classification:
  • The distinction between ALH and LCIS:
    • Is based on the extent of involvement:
      • ALH shows < 50% of acini in the affected TDLU distended by lobular proliferation
      • LCIS shows > 50% of acini in the affected TDLU distended by lobular proliferation with complete filling of at least one lobular unit
    • LCIS is further subdivided into three subtypes:
      • Classic LCIS:
        • Small, monomorphic, non-cohesive cells
        • Typically hormone receptor-positive and HER2-negative
      • Pleomorphic LCIS (PLCIS):
        • Greater nuclear pleomorphism, abundant cytoplasm
        • May be HER2-positive
      • Florid LCIS (FLCIS):
        • LCIS with necrosis and calcifications
• Imaging Diagnosis:
  • Classic lobular neoplasia (ALH and classic LCIS):
    • Is usually not visible on imaging and is typically diagnosed incidentally
    • When imaging abnormalities are present, the most common findings include:
      • Mammography:
        • Grouped amorphous calcifications (most common – 80% of cases)
      • Ultrasound:
        • Irregular, hypoechoic, avascular masses with posterior shadowing (uncommon)
      • MRI:
        • Heterogeneous non-mass-like enhancement with persistent kinetics
  • In contrast, FLCIS and PLCIS are typically imaging targets:
    • Most often manifesting as calcifications (pleomorphic)
  • Scrupulous radiologic-pathologic correlation is essential for appropriate management decisions
• Evidence-Based Management:
  • Management depends on the subtype and radiologic-pathologic concordance:
    • Classic LN (ALH and Classic LCIS) on concordant core biopsy:
      • Surveillance with imaging is now considered safe and appropriate
      • Surgical excision is not routinely required when radiologic-pathologic correlation is concordant
      • Studies show upgrade rates of only 0% to 5% for pure classic LN with concordant imaging
      • One large series showed 3-year conservative management failure rate of only 6.2%, with no same-quadrant cancers developing
      • Indications for surgical excision:
        • Radiologic-pathologic discordance
        • Concurrent high-risk lesions
    • Pleomorphic LCIS:
      • Requires excision:
        • With consideration for negative margins due to high upgrade rates
    • Florid LCIS:
      • Requires complete surgical excision due to high upgrade rates to invasive carcinoma
• Long-term risk management:
  • Annual breast cancer risk of 1% to 2% with LCIS diagnosis
  • Chemoprevention should be recommended to reduce risk
  • Enhanced surveillance:
    • High-risk imaging screening:
      • Annual mammography plus MRI for appropriate candidates
  • Bilateral prophylactic mastectomy is an option for select high-risk patients
  • Upgrade rates vary by study but range from 0% to 13% for classic LN when radiologic-pathologic correlation is performed
  • Most upgrades occur when discordance exists or when other high-risk lesions are present:
    • The decision between surveillance and excision should involve shared decision-making with consideration of personal and family history, patient preferences, and institutional protocols
• References:
  • Lobular Carcinoma in Situ: Diagnostic Criteria and Molecular Correlates. Sokolova A, Lakhani SR. Modern Pathology : An Official Journal of the United States and Canadian Academy of Pathology, Inc. 2021;34(Suppl 1):8-14. doi:10.1038/s41379-020-00689-3.
  • Non-Invasive Lobular Neoplasia: Review and Updates. Tjendra Y, Susnik B. Seminars in Diagnostic Pathology. 2025;42(4):150883. doi:10.1016/j.semdp.2025.150883.
  • Lobular Neoplasia of the Breast Revisited With Emphasis on the Role of E-Cadherin Immunohistochemistry. Dabbs DJ, Schnitt SJ, Geyer FC, et al. The American Journal of Surgical Pathology. 2013;37(7):e1-11. doi:10.1097/PAS.0b013e3182918a2b.
  • Lobular Neoplasia. Lunt L, Coogan A, Perez CB. The Surgical Clinics of North America. 2022;102(6):947-963. doi:10.1016/j.suc.2022.07.001.
  • Recommendations for Women With Lobular Carcinoma in Situ (LCIS). Oppong BA, King TA. Oncology (Williston Park, N.Y.). 2011;25(11):1051-6, 1058.
  • Atypical Hyperplasia of the Breast — Risk Assessment and Management Options. Hartmann LC, Degnim AC, Santen RJ, Dupont WD, Ghosh K. The New England Journal of Medicine. 2015;372(1):78-89. doi:10.1056/NEJMsr1407164.
  • Management of Lobular Neoplasia Diagnosed by Core Biopsy. Jani C, Lotz M, Keates S, et al. The Breast Journal. 2023;2023:8185446. doi:10.1155/2023/8185446.
  • Update on Lobular Neoplasia. Heller SL, Gao Y. Radiographics : A Review Publication of the Radiological Society of North America, Inc. 2023;43(10):e220188. doi:10.1148/rg.220188.
  • Lobular Carcinoma in Situ of the Breast: Clinical, Radiological, and Pathological Correlation. Scoggins M, Krishnamurthy S, Santiago L, Yang W. Academic Radiology. 2013;20(4):463-70. doi:10.1016/j.acra.2012.08.020.
    Atypical Ductal Hyperplasia and Lobular Neoplasia: Update and Easing of Guidelines. Lewin AA, Mercado CL. AJR. American Journal of Roentgenology. 2020;214(2):265-275. doi:10.2214/AJR.19.21991.
  • Society of surgical oncology medical student & trainee primer for breast surgical oncology. Marissa K. Boyle, Julia M. Selfridge, Rachel E. Sargent, et al.
  • Atypical Lobular Hyperplasia and Classic Lobular Carcinoma in Situ Can Be Safely Managed Without Surgical Excision. Laws A, Katlin F, Nakhlis F, et al. Annals of Surgical Oncology. 2022;29(3):1660-1667. doi:10.1245/s10434-021-10827-z.
  • Observation Versus Excision of Lobular Neoplasia on Core Needle Biopsy of the Breast. Schmidt H, Arditi B, Wooster M, et al. Breast Cancer Research and Treatment. 2018;168(3):649-654. doi:10.1007/s10549-017-4629-2.
  • Lobular Intraepithelial Neoplasia: Outcomes and Optimal Management. Boland PA, Dunne EC, Kovanaite A, et al. The Breast Journal. 2020;26(12):2383-2390. doi:10.1111/tbj.14117.

• ESMO 2026 Breast Cancer: 10 Studies to Watch in Madrid
  ESMO Congress 2026 takes place in Madrid, Spain, from 23 to 27 October 2026. OncoDaily picked ten breast cancer abstracts from the official programme. The programme covers both early and advanced disease, with late-breaking phase III trials, mature overall survival (OS) analyses, post-CDK4/6 strategies, biomarker studies and a growing focus on how to sequence antibody–drug conjugates (ADCs). [1]
  Early breast cancer
  1. TALENT (LBA23): T-DXd before surgery in HER2-low, HR+ disease
  This presentation reports final results of a neoadjuvant study testing trastuzumab deruxtecan (T-DXd) with or without anastrozole, or in sequence with chemotherapy, in HER2-low, HR-positive early breast cancer. Earlier data from the phase II trial were presented at SABCS 2022, where investigators stressed that pCR and response results were not yet mature because not all patients had completed scans or surgery. [2, 3]
  2. NATALEE (LBA25): Six-year follow-up of adjuvant ribociclib
  ESMO 2026 will show six-year OS and efficacy outcomes for adjuvant ribociclib plus a nonsteroidal aromatase inhibitor in HR+/HER2− early breast cancer. At the 5-year analysis, invasive disease-free survival was 85.5% with ribociclib plus endocrine therapy versus 81.0% with endocrine therapy alone, a 4.5% absolute improvement. The hazard ratio was 0.716 (95% CI 0.618–0.829). OS data were still immature at that point. [4, 5]
  Advanced HR+/HER2− breast cancer
  3. PANKU-Breast01 (LBA50): iza-bren after prior treatment
  This randomized phase III study tests izalontamab brengitecan in previously treated, unresectable locally advanced or metastatic HR+/HER2− breast cancer. The same drug, an EGFR×HER3 bispecific ADC, already succeeded in triple-negative disease. In the PANKU-Breast02 trial in pretreated TNBC, presented at ASCO 2026, the hazard ratio for PFS was 0.29. Risk of death was 40% lower (HR 0.60; 95% CI 0.42–0.85). [6]
  4. KEYNOTE-B49 (LBA51): Pembrolizumab plus chemotherapy
  This double-blind phase III study compares pembrolizumab with placebo, both added to chemotherapy, in HR+/HER2− advanced breast cancer. It enrolled about 800 patients with PD-L1 CPS ≥1 tumours who had progressed on endocrine therapy and had not received chemotherapy for metastatic disease. These will be the first reported results. [7, 8]
  5. FINER / MA.40 (LBA14): OS with ipatasertib plus fulvestrant
  This presentation reports OS from the randomized phase III trial of fulvestrant plus ipatasertib in ER+/HER2− metastatic breast cancer. The trial randomized 250 patients whose disease had progressed after first-line CDK4/6 inhibitor plus aromatase inhibitor. At ASCO 2025, median PFS was 5.32 months with ipatasertib versus 1.94 months with placebo. In patients with AKT-pathway alterations, median PFS was 5.45 vs 1.91 months (HR 0.47). [9, 10]
  6. VIKTORIA-1 (LBA16): Updated gedatolisib results
  This presentation gives updated results for gedatolisib plus fulvestrant, with or without palbociclib, versus standard of care in HR+/HER2− advanced breast cancer. In the PIK3CA wild-type cohort, median PFS was 9.3 months with the triplet versus 2.0 months with fulvestrant (HR 0.24), and 7.4 months with the doublet (HR 0.33). These results were published in the Journal of Clinical Oncology in March 2026. The FDA has since approved gedatolisib for HR+/HER2−, PIK3CA wild-type advanced breast cancer. [11, 12]
  7. evERA (2RO): Biomarker analyses for giredestrant plus everolimus
  The focus here is retrospective exploratory biomarker analyses, not another efficacy readout. In the primary analysis, median PFS was 8.77 months with giredestrant plus everolimus versus 5.49 months with endocrine therapy plus everolimus (HR 0.56; 95% CI 0.44–0.71). The benefit was larger in ESR1-mutated tumours, with a 62% reduction in risk of progression or death. [13, 14]
  8. postMONARCH (1RO): OS with abemaciclib after a prior CDK4/6 inhibitor
  This presentation reports OS for abemaciclib plus fulvestrant versus placebo plus fulvestrant after progression on a CDK4/6 inhibitor plus endocrine therapy. The primary analysis of 368 patients showed a PFS hazard ratio of 0.73, with median PFS of 6.0 vs 5.3 months. Blinded central review supported this result (HR 0.55). [15, 16]
  Triple-negative disease and ADC sequencing
  9. OptiTROP-Breast01 (4639RO): Final OS for sac-TMT
  This is the final OS analysis of sacituzumab tirumotecan versus chemotherapy in previously treated metastatic TNBC. In the published phase III data, median PFS by central review was 6.7 vs 2.5 months (HR 0.32). At the interim OS analysis, median OS was not reached with sac-TMT versus 9.4 months with chemotherapy (HR 0.53). [17, 18]
  10. SWITCH (4RO): What to do after a first ADC stops working
  This is a prospective phase II platform trial in metastatic breast cancer after prior ADC therapy. It tests switching to a novel ADC with a different target but the same type of payload. No earlier results have been published. [1]
  The bottom line
  Four of these studies bring long-awaited survival data: NATALEE, FINER, postMONARCH and OptiTROP-Breast01. The rest address newer questions, including ADCs in early HER2-low disease, immunotherapy in HR+ disease, treatment after CDK4/6 inhibitors, and what to give after an ADC. The common theme is choosing the right sequence of treatments, not just finding one new active drug.
  References
  Gevorgyan A. ESMO Congress 2026 Breast Cancer: 10 Abstracts to Watch. OncoDaily, 28 Sep 2026. https://oncodaily.com/breast-oncology/esmo-congress-2026-bc
  Hurvitz S, et al. Final results of TALENT. ESMO 2026, LBA23.
  Hurvitz SA, Bardia A, et al. TRIO-US B-12 TALENT. SABCS 2022, GS2-03. https://ascopost.com/news/december-2022/neoadjuvant-t-dxd-shows-clinical-activity-in-patients-with-her2-low-breast-cancer/
  Slamon D, et al. NATALEE 6-year OS. ESMO 2026, LBA25.
  NATALEE 5-year follow-up (PMC); Novartis press release, 17 Oct 2025. https://pmc.ncbi.nlm.nih.gov/articles/12684762 · https://www.novartis.com/news/media-releases/novartis-kisqali-5-year-natalee-data-demonstrate-28-reduction-risk-recurrence-broadest-early-breast-cancer-patient-population
  Lan B, et al. PANKU-Breast01. ESMO 2026, LBA50. PANKU-Breast02 background: https://www.cancernetwork.com/view/izalontamab-brengitecan-improves-os-pfs-in-advanced-metastatic-tnbc
  Rugo H, et al. KEYNOTE-B49. ESMO 2026, LBA51.
  KEYNOTE-B49 trial design (ASCO TPS); ClinicalTrials.gov NCT04895358. https://ace.asco.org/content/370330/abstract/213426
  Redfern A, et al. FINER OS. ESMO 2026, LBA14.
  Chia S, et al. FINER, ASCO 2025. https://www.hmpgloballearningnetwork.com/site/onc/conference-coverage/ipatasertib-plus-fulvestrant-significantly-prolongs-progression-free
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