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• Clarke BL, Khan AA, Rubin MR, et al. Efficacy and safety of TransCon PTH in adults with hypoparathyroidism: 52-week results from the phase 3 PaTHway trial. J Clin Endocrinol Metab. Epub 2024 Oct 8; doi: 10.1210/clinem/dgae693. PMID: 39376010.
• Background:
  • Parathyroid hormone (PTH) serves to maintain calcium phosphate homeostasis:
    • Through its actions on bone, kidney, and the intestines
  • Hypoparathyroidism occurs at an incidence of:
    • 0.8 to 2.6 per 100,000 person-years:
      • With postsurgical hypoparathyroidism being the most common etiology
  • Patients with chronic hypoparathyroidism conventionally have been treated with:
    • Activated vitamin D and oral calcium supplementation to maintain normal calcium levels:
      • They can experience cognitive impairment, renal complications, and extraskeletal calcification
  • PTH replacement therapy:
    • Is of interest to restore normal physiology while mitigating pill burden and complications from conventional treatments of chronic hypoparathyroidism
  • The PaTHway trial:
    • Is an ongoing phase 3 clinical trial of TransCon PTH, or palopegteriparatide:
      • Which is a subcutaneously administered prodrug of PTH (1,23):
        • That releases a sustained level of active PTH over 24 hours, allowing patients with hypoparathyroidism the ability to achieve physiologic levels of active PTH
    • Data from the first 26 weeks of the PaTHway trial, in which 82 enrolled adult patients with chronic hypoparathyroidism were randomly assigned to receive either TransCon PTH or placebo in a double-blind, placebo-controlled clinical trial have previously been reported
    • In the first 26 weeks of this trial, patients were found to have normalization of calcium levels of conventional treatments for hypoparathyroidism and improved health-related quality of life
    • The current publication presents the longer-term outcomes of this trial
• Methods:
  • In the present study, Clarke et al. present the results of the PaTHway trial at 52 weeks of follow-up
  • After the first 26 weeks of the trial, patients were eligible to a 156-week open-label extension (OLE) during which they received dose-adjusted TransCon PTH
  • The primary outcome remained independence from conventional treatment, defined as achieving albumin-corrected calcium in the normal range while not taking activated vitamin D or therapeutic doses of calcium (≤ 600 mg) on the day before the patient’s visit
  • The authors also tracked patient-reported outcomes using the Hypoparathyroidism Patient Experience Scale (HPES) and the 36-Item Short-Form Health Survey (SF-36)
  • The authors assessed longer-term outcomes of patients who were treated with TransCon PTH at baseline and compared results of the patients who were on placebo from baseline to 26 weeks and transitioned to receiving TransCon PTH at 26 weeks when they entered the OLE phase of the trial to patients who were treated with TransCon PTH from the start of the study
• Results:
  • There were 79 participants (60 taking TransCon PTH and 19 placebo) of the initial 82 participants (61 TransCon PTH, 21 placebo) enrolled in the study who completed the first 26-week blinded treatment and entered the OLE:
    • 78 patients completed 52 weeks of the trial (59 TransCon PTH, 19 placebo)
  • The majority of participants enrolled had postsurgical hypoparathyroidism (70 of 82 [85%]) with a mean (±SD) duration of hypoparathyroidism of 11.7±10.7 years
  • Of the 78 participants who received TransCon PTH and completed 52 weeks of the trial, 74 (98%) achieved independence from conventional treatment
  • Patients who were randomly assigned to TransCon PTH at the initiation of the trial had significant improvement in HPES hypoparathyroidism-related symptoms, functioning, and well-being throughout the duration of the trial
  • Patients on placebo at baseline who received TransCon PTH in the OLE at 26 weeks noted similar improvements in HPES score after initiation of TransCon PTH
  • Similar improvements were noted in SF-36 scores
  • Of the 80 patients who received TransCon PTH, 42 (53%) reported treatment-emergent adverse events, which included injection-site reaction (21 patients), nausea (7), headache (6), and hypocalcemia (4) and two serious adverse events related to hypercalcemia that resolved with supportive therapy; all episodes of hypercalcemia were in the first 90 days of treatment and were thought to be related to titration of TransCon PTH dosing
• Conclusions:
  • TransCon PTH is a promising treatment for chronic hypoparathyroidism that can sustain normal calcium levels with daily dosing and mitigate symptoms that impact patient quality of life with minimal risk
• Hypoparathyroidism is the most common complication after thyroidectomy:
  • With rates of permanent hypoparathyroidism ranging from 0.5% to 14.5%
• Although patients with permanent hypoparathyroidism can maintain normal serum calcium levels with activated vitamin D supplementation and / or calcium supplementation, the long-term alteration in PTH physiology and need for calcitriol or calcium can negatively impact patients’ renal function, result in extraskeletal calcification, and result in symptoms that impact their quality of life
• Clarke et al.’s findings present a promising PTH replacement for patients who experience permanent hypoparathyroidism
• In the perioperative setting, both patients and surgeons are often most worried about voice changes and the potential for immediate life-threatening complications, such as postoperative hematoma
• Recent advances in thyroid surgery have allowed for the rates of postoperative recurrent laryngeal nerve injury and postoperative hematoma that necessitate emergent reoperation to be rare occurrences when thyroidectomy is performed by a high-volume thyroid surgeon
• Although permanent hypoparathyroidism after parathyroidectomy does not immediate threaten a patient’s life, it is a chronic health problem for which there has not been a promising therapeutic treatment to addresses the underlaying deficiency in PTH
• With the data of the PaTHway trial demonstrating stable calcium levels and improved patient-reported outcomes once a physiologic dose is achieved, TransCon PTH treatment may enable more routine care along with thyroid hormone replacement at postoperative visits
• Every effort must still be made to preserve parathyroid function, including performing autotransplantation when appropriate; however, TransCon PTH is an encouraging treatment for postoperative hypoparathyroidism
• Key points:
  • In this open-label extension trial of the parathyroid hormone analogue TransCon PTH, palopegteriparatide, for the treatment of hypoparathyroidism, patients initially enrolled in a 26-week randomized controlled trial either continued or were switched to, TransCon PTH
  • Of TransCon PTH–treated participants who completed 52 weeks of the trial, 98% achieved independence from oral treatments
  • Subjects initially randomly assigned to TransCon PTH maintained a quality-of-life benefit throughout the trial, while those switched to TransCon PTH from placebo showed improved symptoms scores after this change
  • These findings provide encouraging data for TransCon PTH treatment for postoperative hypoparathyroidism to reduce dependence on oral supplementation and improve side effects with acceptable adverse effects
• References:
  • Clarke BL. Epidemiology and complications of hypoparathyroidism. Endocrinol Metab Clin North Am 2018;47(4):771-782.
  • Khan AA, Rubin MR, Schwarz P, et al. Efficacy and safety of parathyroid hormone replacement with TransCon PTH in hypoparathyroidism: 26-week results from the phase 3 PaTHway Trial. J Bone Miner Res 2023;38(1):14-25.
  • Clarke BL, Khan AA, Rubin MR, et al. Efficacy and safety of TransCon PTH in adults with hypoparathyroidism: 52-week results from the phase 3 PaTHway trial. J Clin Endocrinol Metab. Epub 2024 Oct 8.
  • Niu A, Zhou L, Papachristos A, et al. Permanent hypoparathyroidism following total thyroidectomy—incidence and preventative strategies without imaging adjuncts. Am J Surg 2025;116196.

The American Society of Clinical Oncology (ASCO) has released updated guidelines on the use of sentinel lymph node biopsy (SLNB) in early breast cancer. The new recommendations are based on high-quality evidence and are designed to support de-escalation of axillary surgery where safe and appropriate. The six main points are:

Omission of SLNB is recommended in postmenopausal women (>50 years) with: Tumors <2 cm Clinically node-negative (cN0) HR-positive, HER2-negative Negative preoperative axillary ultrasound Undergoing breast-conserving surgery with planned whole-breast radiotherapy When SLNB is omitted, it should not influence decisions about radiotherapy or systemic adjuvant therapy. Treatment should still be guided by tumor biology and overall clinical risk. SLNB alone is sufficient in cT1–2N0 patients with 1–2 positive sentinel nodes undergoing breast-conserving surgery with whole-breast radiation. Completion ALND is not necessary. In patients with tumors <5 cm undergoing mastectomy, SLNB with 1–2 positive nodes may also be managed without ALND if postmastectomy radiotherapy is planned. ALND should not be performed in patients with negative SLNB. SLNB remains indicated in specific clinical scenarios: Men with operable breast cancer Pregnancy DCIS patients scheduled for mastectomy Multicentric invasive breast cancer Patients with prior breast or axillary surgery Obese patients Patients with cT3–T4, cN0 disease

Conclusion:

This update reinforces a personalized, evidence-based approach to axillary management in breast cancer. It highlights the importance of:

Ongoing medical education Multidisciplinary coordination Clear physician-patient communication The recommendations aim to reduce unnecessary morbidity from axillary surgery without compromising oncologic outcomes.

Reference:

Boughey JC, Dietz JR, Morrow M, et al. ASCO Guideline Update: Sentinel Lymph Node Biopsy for Patients With Early-Stage Breast Cancer. Journal of Clinical Oncology. 2024;42(12):1343-1355. DOI: 10.1200/JCO.24.00035

• The sodium iodide symporter (NIS) gene:
  • Also known as SLC5A5:
    • Encodes a protein that transports iodide into thyroid follicular cells:
      • This process is crucial for thyroid hormone synthesis
• NIS is a plasma membrane glycoprotein:
  • Located on the basolateral membrane of the thyroid follicular cells
• Mutations in the SLC5A5 gene:
  • Can cause congenital iodide transport defects:
    • Leading to hypothyroidism

• Pendrin, a transporter protein:
  • Is crucial for iodide efflux in thyroid follicular cells:
    • Playing a key role in thyroid hormone synthesis
  • It’s specifically located on the apical membrane of the thyroid follicular cells:
    • Where it mediates the movement of iodide:
      • From inside the cell to the colloid space within the follicle 
• Function:
  • Pendrin acts as a transporter:
    • Facilitating the movement of iodide and chloride ions across the cell membrane
    • In the thyroid, it specifically transports iodide from the cytoplasm of thyroid follicular cells into the follicular lumen (colloid) 
• Location:
  • Pendrin is located on the apical membrane of thyroid follicular cells:
    • Which is the membrane facing the colloid within the thyroid follicle. 
• Significance:
  • This transport is essential for the synthesis of thyroid hormones (T4 and T3)
  • Iodide is first transported into the cell by the:
    •  Sodium-iodide symporter (NIS:
      • Which is located on the basolateral membrane of the thyroid follicular cell
    • Then, pendrin facilitates the efflux of iodide into the colloid:
      • Where it can be used in the synthesis of thyroglobulin (TG)
        • The precursor to thyroid hormones
• Pendred Syndrome:
  • Mutations in the PDS gene, which codes for pendrin:
    • Can lead to Pendred syndrome:
      • A condition characterized by goiter (enlarged thyroid), and hearing loss:
        • Due to impaired iodide transport in the thyroid and inner ear

👉DCIS is noninvasive and, by definition, is unable to metastasize.

👉However, studies have shown that up to 15% of patients with pure DCIS have isolated tumor cells (ITCs) or micrometastasis on nodal evaluation.

– However, these small tumor deposits likely have little prognostic significance and may be cell clusters displaced by biopsy.

👉In patients with DCIS detected by core biopsy, there is a 15% to 20% associated risk of an invasive component when excised.

👉Patients undergoing mastectomy for DCIS should be offered sentinel lymph node biopsy (SLNB) since it would not be feasible to perform following a mastectomy if invasive carcinoma is subsequently identified.

👉ASCO consensus guidelines recommend that patients with DCIS who undergo breast-conserving operation should not routinely have SLNB.

👉However, SLNB could be discussed with patients undergoing breast conservation who have a core biopsy diagnosis of DCIS and a large area of DCIS on imaging (2 to 5 cm), high-grade DCIS, or comedonecrosis or when a physical examination or imaging shows a discrete mass.

👉These findings have been associated with an increased risk of invasive cancer, and SLNB at the time of the initial operation could avoid a second operation.

Training:

• General surgery:

• Michigan State University:

• 2004 al 2010

• Surgical Oncology / Head and Neck Surgery / Endocrine Surgery:

• Fox Chase Cancer Center (Filadelfia):

• 2010 al 2012

• Masters in Science (Clinical research for health professionals):

• Drexel University (Filadelfia):

• 2010 al 2012

• Surgical Oncology / Head and Neck Surgery / Endocrine Surgery:

• IFHNOS / Memorial Sloan Kettering Cancer Center:

• 2014 al 2016

#Arrangoiz

#Surgeon

#Cirujano

#SurgicalOncologist

#CirujanoOncologo

#BreastSurgeon

#CirujanodeMama

#CancerSurgeon

#CirujanodeCancer

• The likelihood of finding invasive cancer on final pathologic evaluation following a core needle biopsy showing DCIS:
  • Has been reported to vary between 10% to 20%:
    • Therefore, a second operation will be required in this subset of patients who are later found to have invasive cancer
• NCCN guidelines recommend:
  • Simultaneous performance of a sentinel lymph node biopsy when operating on patients with DCIS on core biopsy if:
    • The index operation may compromise subsequent lymphatic drainage:
      • Such as a mastectomy or a lumpectomy performed on a cancer in the axillary tail of the breast
• While pathologic subtypes of DCIS may be associated with higher risks of local recurrence:
  • The presence of grade 3 disease and comedonecrosis:
    • Are not associated with higher probabilities of nodal involvement
• Lastly, a history of prior invasive cancer is not associated with a higher probability of invasive cancer when the core biopsy demonstrated DCIS alone

• References
• Jakub JW, Murphy BL, Gonzalez AB, Conners AL, Henrichsen TL, Maimone S 4th, et al. A validated nomogram to predict upstaging of ductal carcinoma in situ to invasive disease. Ann Surg Oncol. 2017;24(10):2915-2924.
• NCCN guidelines Breast Cancer (version 1.2018). National Comprehensive Cancer Network website. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed October 18, 2019.

#Arrangoiz #BreastSurgeon #CancerSurgeon #SurgicalOncologist #BreastCancer #DCIS #SLNB #Miami #Mexico #Surgeon #Teacher

• Lactational or puerperal breast abscesses:
  • Occur in 0.4% to 11% of breastfeeding women
• The objectives of management should include:
  • Resolution of the abscess
  • Relief of pain
  • Continuation of breastfeeding
• Appropriate antibiotic coverage should include:
  • Coverage for Gram-positive organisms until cultures are available to guide therapy
• The most common organisms isolated from cultures include:
  • Staphylococcus aureus
  • Staphylococcus epidermidis
  • Streptococci
• Choice of interventional strategy is somewhat controversial:
  • As both needle aspiration and surgical I&D are highly effective in successfully treating the abscess and have similar recurrence rates
• Needle aspiration:
  • Is associated with reduction of healing time, higher continuation of breastfeeding, and higher patient satisfaction, but the appropriate choice of management depends on the clinical situation
• Aggressive pumping or overfeeding to empty the breast:
  • Can lead to hyperlactation and may contribute to further tissue damage and inflammation:
    • The patient should continue to breastfeed, if possible, or pump physiologic volumes of milk and empty the unaffected breast first
• While mammary fistula (“milk fistula”) is the most common complication after breast abscess:
  • It is relatively rare, occurring in 1% to 3% of patients
  • They can develop spontaneously:
    • But more commonly occur after instrumentation of the breast (eg, needle biopsies, aspirations, surgery)
    • Not surprisingly, incidence of milk fistula after needle aspiration is significantly lower than surgical I&D for women with lactational breast abscesses (RR=0.21, p=0.013)
  • For patients undergoing surgery:
    • Incisions should be as small and as far from the nipple-areolar complex as possible
    • Placement of closed-suction drains or vacuum-assisted dressings should be avoided:
      • As they may promote fistula development due to granulation tissue formation:
        • Penrose drain or another non-suction drain should be used instead
    • While dopamine agonists have been shown to effectively cease lactation:
      • They are no longer routinely recommended
    • Continued breastfeeding is encouraged and can divert milk flow through the nipple, minimizing flow through the cavity
• References:
  • Zhou F, Li Z, Liu L, et al. The effectiveness of needle aspiration versus traditional incision and drainage in the treatment of breast abscess: a meta-analysis. Ann Med. 2023;55(1):2224045. Published online June 23, 2023. doi: 10.1080/07853890.2023.2224045
  • Mitchell K, Johnson H, Rodriguez J, et al; Academy of Breastfeeding Medicine.  Academy of Breastfeeding Medicine Clinical Protocol #36: The Mastitis Spectrum, Revised 2022.  Breastfeed Med. 2022;17(5):360-376. doi: 10.1089/bfm.2022.29207.kbm
  • Johnson HM, Mitchell KB.  Low incidence of milk fistula with continued breastfeeding following radiologic and surgical interventions on the lactating breast. Breast Dis. 2021;40(3):183-189. doi: 10.3233/BD-201000

• Lactational breast abscesses:
  • Develop in up to a quarter of all breastfeeding women:
    • Typically within the first 12 weeks after birth or during the weaning process
• Breast abscesses:
  • Rarely resolve with antibiotics alone
• Abscesses generally require:
  • Drainage in conjunction with antibiotics
• Depending on the prevalence of community-acquired MRSA in the region in which the patient presents:
  • MRSA coverage may be empirically initiated
• A recent Cochrane review:
  • Found insufficient evidence to determine whether:
    • Needle aspiration is a more effective option to incision and drainage (I&D) for lactational breast abscesses, or whether an antibiotic should be routinely added to women undergoing I&D for lactational breast abscesses
    • The evidence for the primary outcome of treatment failure is low quality, with downgrading based on including small studies with few events and unclear risk of bias
• The American Society of Breast Surgeons:
  • Has recommended an attempt at needle aspiration as first-line treatment for a breast abscess
• Compared to operative incision and drainage:
  • Fine needle aspiration offers decreased morbidity
• References:
  • Rao R, Ludwig K, Bailey L, Berry TS, Buras R, Degnim A, et al. Select choices in benign breast disease: an initiative of the American Society of Breast Surgeons for the American Board of Internal Medicine Choosing Wisely^® Campaign. Ann Surg Oncol. 2018;25(1):2795-2800.
  • Boakes E, Woods A, Johnson N, Kadoglou N. Breast infection: a review of diagnosis and management practices. Eur J Breast Health. 2018;14(3):136-143.
  • Irusen H, Rohwer AC, Steyn DW, Young T. Treatments for breast abscesses in breastfeeding women. Cochrane Database Syst Rev. 2015(8):CD010490.

#Arrangoiz #BreastSurgeon #CancerSurgeon #SurgicalOncologist #LactationalBreastAbcesses #Miami #Mexico #Teacher

• In accordance with National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines:
  • Patients that converted from clinically node positive to negative on both physical exam and imaging after neoadjuvant chemotherapy:
    • Are candidates for targeted axillary dissection (TAD)
• In order to minimize the false negative rate of TAD:
  • It is important to retrieve the:
    • Clipped malignant axillary lymph node and also perform a sentinel lymph node biopsy (SLNB)
• Data from ACOSOG Z1071 and MD Anderson Cancer Center:
  • Demonstrated false negative rates greater than approximately 10% to 20% with SLNB alone
  • These rates decreased to nearly 1% to 7%:
    • With the addition of a directed retrieval of the initially malignant axillary lymph node
• Despite the excellent response to neoadjuvant chemotherapy (NACT) on exam and imaging:
  • There is no data to support non-operative management of the axilla in this patient who presented with regionally advanced invasive breast cancer
• Unlike with an upfront surgery approach:
  • Any residual disease in the axillary lymph nodes after NACT:
    • Warrants completion level I / II axillary lymph node dissection:
      • In fact, studies have shown rates of additional axillary disease:
        • Ranging from about 30% to 60% in patients with residual micrometastases after NACT
        • These rates are greater than the residual axillary disease rate in ACOSOG Z0011 and also suggest disease that is resistant to systemic therapy and in need of regional control
• There is no role for random sampling of additional level one axillary lymph nodes
• Furthermore, while nomograms exist to predict the probability of detecting additional positive non-sentinel lymph nodes in this setting and occasionally special circumstances exist that warrant discussion of results with the patient and one’s colleagues before moving forward:
  • Completion level I / II ALND at the time of the index surgery remains the standard of care
• The results of Alliance 11202:
  • A randomized phase III trial comparing axillary lymph node dissection to axillary radiation in breast cancer patients (cT1 to cT3, cN1) who have positive sentinel lymph node disease after receiving neoadjuvant chemotherapy will help address the question of whether regional node irradiation is equivalent to cALND plus regional node radiation with respect to recurrence-free survival
• It should also be noted that the OPBC-04 /Eubreast-06 study:
  • Examined oncologic outcomes following omission of axillary lymph node dissection in node positive patients downstaging to node negative with neoadjuvant chemotherapy
  • Axillary recurrence after omission of ALND in patients who successfully downstage from N+ to ypN0 with NAC is a rare event following both SLNB or TAD, and was not significantly different between those who underwent a TAD versus SLNB
  • The 3-year axillary recurrence rate was less than 1% with TAD or SLNB, while locoregional recurrence at 3 and 5 years was 1.5% and 2.7%, respectively, in all patients and did not differ significantly with the two strategies of lymph node re-staging
• Furthermore, when the SLNB procedure is optimized with dual tracer and retrieval of ≥ 3 SLNs, the clipped node is an SLN in the majority of cases:
  • Suggesting that failure to retrieve the clipped node should not be an indication for ALND
• References
  • Boughey JC, Ballman KV, Le-Petross HT, et al. Identification and Resection of Clipped Node Decreases the False-negative Rate of Sentinel Lymph Node Surgery in Patients Presenting With Node-positive Breast Cancer (T0-T4, N1-N2) Who Receive Neoadjuvant Chemotherapy: Results From ACOSOG Z1071 (Alliance). Ann Surg. Apr 2016;263(4):802-7. doi:10.1097/SLA.0000000000001375 
  • Caudle AS, Yang WT, Krishnamurthy S, et al. Improved Axillary Evaluation Following Neoadjuvant Therapy for Patients With Node-Positive Breast Cancer Using Selective Evaluation of Clipped Nodes: Implementation of Targeted Axillary Dissection. J Clin Oncol. Apr 01 2016;34(10):1072-8. doi:10.1200/JCO.2015.64.0094 
  • Moo TA, Edelweiss M, Hajiyeva S, et al. Is Low-Volume Disease in the Sentinel Node After Neoadjuvant Chemotherapy an Indication for Axillary Dissection? Ann Surg Oncol. Jun 2018;25(6):1488-1494. doi:10.1245/s10434-018-6429-2 
  • Weiss A, King C, Vincuilla J, et al. Rates of pathologic nodal disease among cN0 and cN1 patients undergoing routine axillary ultrasound and neoadjuvant chemotherapy. Breast Cancer Res Treat. Sep 2022;195(2):181-189. doi:10.1007/s10549-022-06677-2 
  • Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. Feb 9 2011;305(6):569-75. doi:10.1001/jama.2011.90 
  • Montagna G, Lee MK, Sevilimedu V, Barrio AV, Morrow M. Is Nodal Clipping Beneficial for Node-Positive Breast Cancer Patients Receiving Neoadjuvant Chemotherapy? Ann Surg Oncol. 2022 Oct;29(10):6133-6139. doi: 10.1245/s10434-022-12240-6. Epub 2022 Jul 28. PMID: 35902495; PMCID: PMC10109537.

• The management of breast cancer:
  • Has become increasingly complex and multidisciplinary:
    • With increasing imaging studies, appointments, and often, second or third opinions patients seek for care
  • Together, many of these factors have led to lengthening time intervals between diagnosis and surgery
• At the same time, time from diagnosis to surgical treatment of 60 days:
  • Is now a Commission on Cancer quality metric
• Minimizing delays in treatment:
  • Is a sensible goal believed to lead to improved outcomes
• The precise time frame that is considered reasonable and safe versus detrimental to breast cancer survival is not known:
  • Although a number of recent large retrospective studies have evaluated this
• Bleicher et al:
  • In a 2016 study of nearly 100,000 women > age 65 in the SEER-Medicare database:
    • Showed that overall survival decreased by 9% after a 60-day delay from diagnosis to surgery
  • In addition, the association between overall survival and time to surgery:
    • Was significant for stage I (HR 1.13, p<0.001) and stage II (HR 1.06, p<0.01):
      • But not for stage III breast cancer patients
  • The association between breast cancer-specific survival and time to surgery (HR 1.84, p=0.02):
    • Persisted solely for stage I patients:
      • Likely attributable to the baseline mortality in this group being smaller than the relative impact imposed by a delay in treatment
• A 2020 study of ~350,000 patients (of all ages) in the NCDB with stage I to III breast cancer treated with up front surgical therapy examined the relationship between overall survival, time to surgery, and biologic subtype of breast cancer (i.e. triple negative, ER+PR+, HER2+):
  • Prevailing opinion prior to this study was that delays would be more detrimental to those with more biologically aggressive tumors such as TN or HER2+ due to downstream delays in adjuvant systemic therapy resulting from delayed surgical treatment
  • This study found that overall survival was observed to decline with every month delay in surgical treatment (HR 1.1, p<0.001), and this did not vary by biologic subtype (p>0.33)
• A more recent 2023 study of NCDB stage I to III breast cancer patients treated with up front surgery analyzed survival for every one-week interval after 30 days post-diagnosis:
  • Median time to surgery was 30 days:
    • 90% of patients underwent surgery within 60 days
  • Delays of 9 weeks or greater:
    • Were found to be more common in younger women and the uninsured
  • They found that there was no significant association between time to surgery and survival:
    • For any of the groups until after 9 weeks post-diagnosis
  • A surgical delay of 9 weeks or longer after diagnosis was associated with worse overall survival (HR 1.15, p < 0.001) compared with surgery within 4 weeks of diagnosis
  • Again, no significant interaction was found between tumor biologic subtype and time to surgery’s association with survival
  • Therefore, the conclusion was made that 8 weeks or shorter serve as a standard quality metric for timeliness of surgery
• References:
  • Bleicher RJ et al. Preoperative delays in the US Medicare population with breast cancer. J Clin Oncol 2012; 30:4485-92
  • Bleicher RJ et al. Time to Surgery and Breast Cancer Survival in the United States. JAMA Surg 2016; 2:330-9
  • Mateo AM et al. Time to Surgery and the Impact of Delay in the Non-Neoadjuvant Setting on Triple-Negative Breast Cancers and Other Phenotypes. Ann Surg Oncol 2020; 27:1679-92
  • Wiener AA et al. Reexamining Time From Breast Cancer Diagnosis to Primary Breast Surgery. JAMA Surg 2023; 158:485-92