A Prospective Study of Sentinel Node Biopsy Omission in Women Age ≥ 65 Years with ER+ Breast Cancer.

BACKGROUND: National guidelines recommend omitting SNB in older patients with favorable invasive breast cancer. However, there is a lack of prospective data specifically addressing this issue. This study evaluates recurrence and survival in estrogen receptor-positive/Her2- (ER+) breast cancer patients, aged ≥ 65 years who have breast-conserving surgery (BCS) without SNB. METHODS: This is a prospective, observational study at a single institution where 125 patients aged ≥ 65 years with clinical T1-2N0 ER+ invasive breast cancer undergoing BCS were enrolled. Patients were treated with BCS without SNB. Primary outcome measure was axillary recurrence. Secondary outcome measures include recurrence-free survival (RFS), disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS). RESULTS: From January 2016 to July 2022, 125 patients were enrolled with median follow-up of 36.7 months [95% confidence interval (CI) 35.0-38.0]. Median age was 77.0 years (range 65-93). Median tumor size was 1 cm (range 0.1-5.0). Most tumors were ductal (95/124, 77.0%), intermediate grade (60/116, 51.7%), and PR-positive (117/123, 91.7%). Radiation therapy was performed in 37 of 125 (29.6%). Only 60 of 125 (48.0%) who were recommended hormonal therapy were compliant at 2 years. Chemotherapy was administered to six of 125 (4.8%) patients. There were two of 125 (1.6%) axillary recurrences. Estimated 3-years rates of regional RFS, DFS, and OS were 98.2%, 91.2%, and 94.8%, respectively. Univariate Cox regression identified hormonal therapy noncompliance to be significantly associated with recurrence (p = 0.02). CONCLUSIONS: Axillary recurrence rates were extremely low in this cohort. These results provide prospective data to support omission of SNB in this patient population TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02564848.

Exploring potential use of internet, E-mail, and instant text messaging to promote breast health and mammogram use among immigrant Hispanic women in Los Angeles County.

Breast cancer is now the leading cause of death in Hispanic women (HW). Internet, e-mail, and instant text messaging may be cost-effective in educating HW about breast health and in reducing breast cancer mortality. We surveyed 905 HW women attending a free health fair about their technology use, acculturation, insurance status, mammography use, and breast cancer knowledge. Data were analyzed by t test or χ(2) tests. Mean age was 51.9 ± 14.2 years (range, 18 to 88 years). Ninety-two per cent were foreign-born. Most had completed some high school (39%) or elementary (38%) education. Most (62%) were uninsured. The majority spoke (67%) and read (66%) only Spanish. Only 60 per cent of HW older than 40 years had a recent mammogram. HW older than 40 years who had not had a recent mammogram were younger (mean 54.9 ± 10.8 vs 58 ± 10.4 years) and less likely to have health insurance (25 vs 44%; P < 0.001). Most HW never use the Internet (58%) or e-mail (64%). However, 70 per cent have mobile phones (66% older than 40 years), and 65 per cent use text messaging daily (58% older than 40 years, P = 0.001). In fact, 45 per cent wish to receive a mammogram reminder by text. Text messaging may be an inexpensive way to promote breast health and screening mammography use among uninsured HW.

Paget's disease of the nipple with parenchymal ductal carcinoma in situ is associated with worse prognosis than Paget's disease alone.

Paget's disease of the nipple is often found in conjunction with underlying ductal carcinoma in situ (DCIS). In isolation, Paget's disease of the nipple, like DCIS, confers an excellent prognosis for survival. Our objective was to determine if Paget's disease identified with synchronous parenchymal DCIS has as favorable an outcome as Paget's disease alone. We analyzed a prospectively maintained pathology database and medical records to identify all patients diagnosed with Paget's disease of the nipple between June 1996 and December 2011. Overall survival was analyzed using Kaplan-Maier statistics and Cox proportional hazards modeling. Seventy-four patients were identified with Paget's disease: five (6%) with isolated Paget's of the nipple, 22 (30%) associated with parenchymal DCIS, and 47 (64%) associated with invasive cancer (± DCIS). Unexpectedly, patients with Paget's disease and DCIS had a worse prognosis than those with Paget's disease alone. Survival correlated with pathologic stage at diagnosis. Among the 16 deaths, median survival was 2.8 years (range, 0.1 to 15.2 years). Median follow-up for the entire cohort was 4.2 years (range, 0.1 to 15.2 years). Thus, Paget's disease with parenchymal DCIS may confer worse survival than isolated Paget's disease of the nipple, suggesting the difficulty of identifying invasive carcinoma within a background of DCIS.

Postmastectomy radiation of latissimus dorsi myocutaneous flap reconstruction is well tolerated in women with breast cancer.

Chest wall irradiation decreases locoregional recurrence and breast cancer-related mortality in women at high risk for recurrence after mastectomy. Many women undergoing mastectomy desire immediate breast reconstruction. Postmastectomy radiation therapy (PMRT), however, increases the risk of surgical complications and may adversely affect the reconstructed breast. We compared outcomes of immediate latissimus dorsi myocutaneous flap (Lat Flap) versus tissue expander/implant (EI) reconstruction after mastectomy followed by PMRT in 29 women with invasive breast cancer treated at a single institution between 2009 and 2011. Although patients undergoing EI reconstruction were slightly younger and more frequently underwent bilateral mastectomy, there were no major differences between the groups with respect to patient or tumor characteristics. With a median follow-up of 11 months (Lat Flap) and 13 months (EI) after completion of PMRT, there was a trend toward more wound complications requiring reoperation, including expander/implant loss (n=3), in the EI group. Capsular contracture was the most common sequela of PMRT in the Lat Flap group (67%) but this was easily treated with capsulotomy at the time of nipple-areola reconstruction. Immediate breast reconstruction with a latissimus dorsi myocutaneous flap is a viable option for women undergoing mastectomy who are likely to require chest wall irradiation.

Discordance between pathologic and radiologic tumor size on breast MRI may contribute to increased re-excision rates.

Preoperative breast MRI does not decrease re-excision rates in patients who undergo lumpectomy. We evaluated concordance of tumor size on MRI and pathologic size in patients who underwent re-excision of margins after lumpectomy. A retrospective review of patients at the Cedars-Sinai Breast Center who received breast MRI was performed. We found that MRI was performed before lumpectomy in 136 patients. Mean age was 55.2 years (standard deviation ± 12.6). Re-excision occurred in 34 per cent (n = 46). Of those undergoing re-excision, 35 per cent (16/46) were re-excised for ductal carcinoma in situ (DCIS) at the lumpectomy margin. There was no significant difference between radiologic and pathologic size of the tumor (1.94 vs 2.12 cm; P = 0.159). In those who underwent re-excision, the radiologic size was underestimated compared with the pathologic size (2.01 vs 2.66 cm; P = 0.032). Patients with pure DCIS lesions (n = 9) also had smaller radiologic tumor size compared with pathologic (0.64 vs 2.88 cm; P = 0.039), and this difference trended toward significance in those who underwent re-excision (0.55 vs 3.50 cm; P = 0.059). Discordance between tumor size on MRI and pathologic size may contribute to re-excisions in patients who undergo lumpectomy. The limitations of breast MRI to evaluate the extent of DCIS surrounding many breast cancers, and the impact on re-excision rates, should be further evaluated.

Breast MRI after bilateral mastectomy: is it indicated?

Little is known about the use of breast MRI as a diagnostic or surveillance tool in patients after bilateral mastectomy. The objective of this study was to evaluate breast MRI after bilateral mastectomy. Participants consisted of 48 women with prior bilateral mastectomy who underwent breast MRI between 2003 and 2009. Seventy-nine breast MRIs were obtained. The median time between mastectomy and first MRI was 36 months. MRI was ordered most often by a medical oncologist (71%). Median age at bilateral mastectomy was 49 years (range, 33 to 72 years). Reasons for obtaining MRI included surveillance in 60 (76%), mass in eight (10%), lymph nodes in four (5%), pain in three (4%), and abscess in one (1%). Overall, 68 (86%) MRIs showed benign imaging findings only. Within the surveillance group, six patients had MRIs with findings that changed management; four patients had some residual breast tissue, and two patients had findings outside the breast that were better evaluated by CT or bone scan and were ultimately benign. MRI confirmed locoregional recurrence in two patients with highly suspicious physical findings. Overall, postmastectomy breast MRI had limited use, finding no unsuspected recurrences within our study group. Although MRI can be helpful to establish the presence of residual breast tissue after bilateral mastectomy, subsequent routine screening breast MRI should be questioned if no residual breast tissue is identified.

Increased use of MRI for breast cancer surveillance and staging is not associated with increased rate of mastectomy.

The use of MRI in preoperative staging of breast cancer has escalated recently. Breast MRI has greater sensitivity than mammography, ultrasound, and clinical examination in cancer detection. Because of its variable specificity, however, there has been concern that increased MRI use will result in increased rates of mastectomy for early-stage breast cancer. We postulated that mastectomy rates are not affected by trends in MRI use. We performed a retrospective analysis of imaging tests ordered by surgeons at our breast center from 2003 to 2007. We also reviewed all breast cancer cases reported to the National Cancer Database from our institution during the same time period and categorized them as having been treated with mastectomy or breast-conserving surgery. From 2003 to 2007, the number of breast MRIs ordered annually by surgeons increased from 68 to 358. The rate of MRI use increased from 4.1 per every 100 patients seen to 5.7 and from 1.6 per every 100 new patients seen to 2.9. The percentage of women undergoing mastectomy for breast cancer remained unchanged during this 5-year interval. Therefore, although MRI use in breast cancer staging and surveillance has increased, mastectomy rates have not.

A 2-minute pre-extubation protocol for ventilated intensive care unit patients.

BACKGROUND: Clinicians often are challenged with safely predicting the optimal time of extubation for ventilated patients. Commonly used weaning parameters have poor positive predictive value for successful extubation. METHODS: A total of 213 intubated patients in our 20-bed surgical intensive care unit were enrolled in a trial to test a prospective, observational, 2-minute extubation protocol (TMEP). Daily measurements were obtained on all intubated patients who met criteria, which included adequate oxygenation, systolic blood pressure, heart rate, hemoglobin, Glasgow Coma Score greater than 10t, absence of significant metabolic/respiratory acidosis, and absence of therapeutic or neurologic paralysis. During TMEP, endotracheally intubated patients were physically disconnected from the ventilator for a 2-minute period of observation while spontaneously breathing room air. Patients were extubated if they tolerated the trial without clinically significant desaturation or alteration of vital signs or mental status. RESULTS: The TMEP reliably predicted successful extubations in 203 of 213 patients (95.3%). Patients who required reintubation had a longer intensive care unit stay and a longer hospital stay. CONCLUSIONS: TMEP is a simple and reliable method of predicting successful extubation.

Scarless fetal wounds are associated with an increased matrix metalloproteinase-to-tissue-derived inhibitor of metalloproteinase ratio.

In contrast to adult cutaneous wounds, early fetal wounds heal scarlessly. Fetal rat skin transitions from scarless repair to healing, with scar formation between days 16.5 (E16) and 18.5 (E18) of gestation. Term gestation is 21.5 days. The composition of the extracellular matrix in fetal skin and wounds differs from that of the adult. Matrix metalloproteinases (MMPs) and their tissue-derived inhibitors (TIMPs) determine the architecture of the extracellular matrix. The authors hypothesized that differential expression of MMPs and TIMPs occurs during the ontogenetic transition to scar-forming repair in fetal skin and wounds. Full-thickness, excisional wounds (2 mm) were created on the dorsum of E16 (n = 42 fetuses) and E19 fetal rats (n = 42 fetuses). Wounds were harvested at 24, 48, and 72 hours. Nonwounded skin from littermates was also harvested as controls. Six E16 and E19 wounds were fixed 72 hours after injury, stained with hematoxylin and eosin, and examined by light microscopy. RNA was isolated from the remaining wounds and skin, and a reduced-cycle, primer-specific, reverse-transcriptase polymerase chain reaction was performed to semiquantitatively determine relative gene expression of MMP-1, MMP-2, MMP-7, MMP-9, and MMP-14 and of TIMP-1, TIMP-2, and TIMP-3. Significance was determined by unpaired two-tailed t test (p < 0.05) and analysis of variance. In both E16 and E19 wounds, reepithelialization was complete by 72 hours. E16 wounds healed scarlessly, whereas E19 wounds healed with scar. During late gestation, skin expression of MMP-1 and MMP-14 (membrane type-1 MMP) doubled, whereas MMP-2 expression increased nearly 50-fold. Levels of MMP-7 and MMP-9 were unchanged in developing skin. As for the TIMPs, skin expression of TIMP-2 increased more than four-fold, whereas TIMP-1 and TIMP-3 expression was unchanged. In both scarless and scarring wounds, up-regulation of MMP-1 and MMP-9 occurred. However, the maximal increase in MMP-1 and MMP-9 expression occurred much more rapidly and was much greater in the scarless E16 wounds (28-fold versus 23-fold for MMP-1 and 18-fold versus nine-fold for MMP-9). Unchanged in scarless wounds, MMP-2 levels decreased more than three-fold in scarring wounds. MMP-14 (membrane type-1 MMP) expression increased three-fold in scarless wounds but was unchanged in scarring wounds. In contrast, TIMP-1 and TIMP-3 expression in E19 scarring wounds increased six-fold and four-fold, respectively. MMP-7 and TIMP-2 expression did not change in response to injury. E16 scarless wounds have greater MMP relative to TIMP expression than E19 scarring wounds. This favors extracellular matrix turnover, facilitates migration of fetal cells, and promotes scarless repair.

Decreased expression of fibroblast and keratinocyte growth factor isoforms and receptors during scarless repair.

Fibroblast growth factors (FGFs) are a family of 21 cytokines with a broad spectrum of activities, including regulation of cell proliferation, differentiation, and migration. The various FGFs bind to one or more of four different tyrosine kinase receptor types. FGFs 1, 2, 5, 7, and 10 are up-regulated during adult cutaneous wound healing. However, the expression of FGFs during fetal skin development and scarless wound healing has not been characterized. It was hypothesized that differential expression of FGF isoforms and receptors occurs during fetal skin development and that this differential expression pattern may regulate the transition from scarless repair to healing with scar formation. Excisional wounds (2 mm) were created on fetal rats at gestational days 16.5 (scarless) (one wound per fetus, n = 36 fetuses) and 19.5 (scarring) (one wound per fetus, n = 36 fetuses). Wounds were harvested at 24, 48, and 72 hours. Survival until wound harvest ranged from 66 to 75 percent for the gestational day 16 fetuses, and from 83 to 92 percent for the gestational day 19 fetuses. Nonwounded fetal skin from littermates (n = 12 fetuses per wound harvest time point) was used as the control. Wounds/skins were pooled by harvest time point, and RNA was isolated from pooled wounds/skins. Reduced-cycle, specific-primer reverse transcriptase-polymerase chain reaction was performed to determine the expression of FGF isoforms 2, 5, 7, 9, and 10 and FGF receptors 1, 2, and 4 in wounds relative to unwounded skin.In unwounded fetal skin, FGF isoform 5 expression more than doubled at birth. FGF 10 expression doubled during the transition period. FGF 7 expression increased more than sevenfold at birth. Expression of FGF isoforms 2 and 9 did not change during late fetal skin development. The expression of FGF receptors 1, 2, and 4 increased at birth. After wounding, expression of FGF isoforms 7 and 10 was down-regulated in scarless wounds, whereas FGF receptor 2 expression decreased in both scarless and scar-forming wounds. Expression of FGF isoforms 5 and 9 did not change in scarless wounds. FGF receptor 2 expression was down-regulated in both scarless and scarring wounds, but at an earlier and more sustained level in scarless wounds. Receptor type 4 expression increased in scarring wounds, whereas type 1 expression did not change in either scarless or scarring wounds. These results demonstrate an overall down-regulation of FGF expression during scarless healing.

Confocal microscopic analysis of scarless repair in the fetal rat: defining the transition.

Fetal wounds pass from scarless repair to healing with scar formation during gestation. This transition depends on both the size of the wound and the gestational age of the fetus. This study defines the transition period in the fetal rat model and provides new insight into scarless collagen wound architecture by using confocal microscopy. A total of 16 pregnant Sprague-Dawley rats were operated on. Open full-thickness wounds, 2 mm in diameter, were created on fetal rats at gestational ages 14.5 days (E14; n = 10), 16.5 days (E16; n = 42), and 18.5 days (E18; n = 42) (term = 21.5 days). Wounds were harvested at 24 (n = 18 per gestational age) and 72 hours (n = 24 per gestational age). Skin at identical gestational ages to wound harvest was used for controls. The wounds were fixed and stained with hematoxylin and eosin, antibody to type I collagen, and Sirius red for confocal microscopic evaluation. No E14 rat fetuses survived to wound harvest. Wounds created on E16 fetal rats healed completely and without scarring. E16 fetal rat hair follicle formation and collagen architecture was similar to that of normal, nonwounded skin. Wounds created on E18 fetal rats demonstrated slower healing; only 50 percent were completely healed at 72 hours compared with 100 percent of the E16 fetal rat wounds at 72 hours. Furthermore, the E18 wounds healed with collagen scar formation and without hair follicle formation. Confocal microscopy demonstrated that the collagen fibers were thin and arranged in a wispy pattern in E16 fetal rat wounds and in nonwounded dermis. E18 fetal rat wounds had thickened collagen fibers with large interfiber distances. Two-millimeter excisional E16 fetal rat wounds heal without scar formation and with regeneration of normal dermal and epidermal appendage architecture. E18 fetal rat wounds heal in a pattern similar to that of adult cutaneous wounds, with scar formation and absence of epidermal appendages. Confocal microscopy more clearly defined the dermal architecture in normal skin, scarless wounds, and scars. These data further define the transition period in the fetal rat wound model, which promises to be an effective system for the study of in vivo scarless wound healing.