Surgical treatment of breast cancer in previously augmented patients

The incidence of breast cancer is increasing each year. Concomitantly, cosmetic breast augmentation has become the second most often performed cosmetic surgical procedure. As the augmented patient population ages, an increasing number of breast cancer cases among previously augmented women can be anticipated. The surgical treatment of these patients is controversial, with several questions remaining unanswered. Is breast conservation therapy feasible in this patient population and can these patients retain their implants? A retrospective review of all breast cancer patients with a history of previous augmentation mammaplasty who were treated at the Revlon/UCLA Breast Center between 1991 and 2001 was performed. During the study period, 58 patients were treated. Thirty patients (52 percent) were treated with a modified radical mastectomy with implant removal. Twenty-eight patients (48 percent) underwent breast conservation therapy, which consisted of lumpectomy, axillary lymph node dissection, and radiotherapy. Twenty-two of the patients who underwent breast conservation therapy initially retained their implants. Eleven of those 22 patients (50 percent) ultimately required completion mastectomies with implant removal because of implant complications (two patients), local recurrences (five patients), or the inability to obtain negative margins (four patients). Nine additional patients experienced complications resulting from their implants, including contracture, erosion, pain, and rupture. The data illustrate that breast conservation therapy with maintenance of the implant is not ideal for the majority of augmented patients. Breast conservation therapy with explantation and mastopexy might be appropriate for rare patients with large volumes of native breast tissue. Mastectomy with immediate reconstruction might be a more suitable choice for these patients.     

The effect of breast implants on the radiographic detection of microcalcification and soft-tissue masses

Current implants for breast augmentation containing silicone gel, saline, or both can totally obscure mammographic detection of microcalcifications and soft-tissue masses. To investigate the possibility of developing a more radiolucent implant, radiographs were obtained of silicone shells that contained silicone gel, saline, silicone gel and saline, polyurethane-covered silicone gel, gelatin, sunflower oil, and peanut oil. All radiographs were obtained using a Siemens Mammomat by placing the implant over an American College of Radiology mammography phantom. Results were measured by the ability to visualize or resolve the artifacts in the mammography phantom. The silicone shell alone minimally altered artifact resolution. Silicone shells filled with silicone gel, silicone gel and saline, saline alone, polyurethane-covered silicone gel, and gelatin were equal in radiodensity and completely obscured all phantom artifacts. Silicone shells filled with peanut oil and sunflower oil had equal radiodensity and allowed visualization of large microcalcifications and some soft-tissue masses. Current implants used for augmentation mammaplasty can totally obscure mammographic detection of microcalcifications and soft-tissue masses. A more radiolucent breast implant is possible, and further research is needed to define the best filler material and test its biocompatibility.     

Area and Volumetric Density Estimation in Processed Full-Field Digital Mammograms for Risk Assessment of Breast Cancer

Introduction

Mammographic density, the white radiolucent part of a mammogram, is a marker of breast cancer risk and mammographic sensitivity. There are several means of measuring mammographic density, among which are area-based and volumetric-based approaches. Current volumetric methods use only unprocessed, raw mammograms, which is a problematic restriction since such raw mammograms are normally not stored. We describe fully automated methods for measuring both area and volumetric mammographic density from processed images.

Methods

The data set used in this study comprises raw and processed images of the same view from 1462 women. We developed two algorithms for processed images, an automated area-based approach (CASAM-Area) and a volumetric-based approach (CASAM-Vol). The latter method was based on training a random forest prediction model with image statistical features as predictors, against a volumetric measure, Volpara, for corresponding raw images. We contrast the three methods, CASAM-Area, CASAM-Vol and Volpara directly and in terms of association with breast cancer risk and a known genetic variant for mammographic density and breast cancer, rs10995190 in the gene ZNF365. Associations with breast cancer risk were evaluated using images from 47 breast cancer cases and 1011 control subjects. The genetic association analysis was based on 1011 control subjects.

Results

All three measures of mammographic density were associated with breast cancer risk and rs10995190 (p<0.025 for breast cancer risk and p<1×10⁻⁶ for rs10995190). After adjusting for one of the measures there remained little or no evidence of residual association with the remaining density measures (p>0.10 for risk, p>0.03 for rs10995190).

Conclusions

Our results show that it is possible to obtain reliable automated measures of volumetric and area mammographic density from processed digital images. Area and volumetric measures of density on processed digital images performed similar in terms of risk and genetic association.     

Breast Reconstruction for Malignant or Premalignant Disease

In ten patients breast reconstruction was done after surgical treatment for a premalignant or malignant breast disease. In six of these, prophylactic subcutaneous mastectomy and implant reconstruction were carried out, and in the remaining four reconstruction was done after simple or modified radical mastectomy. It is suggested that these procedures should be considered by those physicians and surgeons who undertake evaluation and treatment of breast disease in women. Breast reconstruction should be considered and offered to patients who suffer from the severe personal and emotional trauma attendant to surgical operation for breast disease.     

An improved technique for creation of the inframammary fold in silicone implant breast reconstruction.

A "lipo-fascial" flap is described for creation of the inframammary fold in patients undergoing breast reconstruction with silicone implants. We have employed this technique in 13 patients. The fold has been enhanced in all cases, and we have not encountered any significant complications. This technique is a useful adjunct to breast reconstruction with a silicone implant, and we recommend that it be considered in appropriate patients.     

Agreement of Mammographic Measures of Volumetric Breast Density to MRI

Background

Clinical scores of mammographic breast density are highly subjective. Automated technologies for mammography exist to quantify breast density objectively, but the technique that most accurately measures the quantity of breast fibroglandular tissue is not known.

Purpose

To compare the agreement of three automated mammographic techniques for measuring volumetric breast density with a quantitative volumetric MRI-based technique in a screening population.

Materials and Methods

Women were selected from the UCSF Medical Center screening population that had received both a screening MRI and digital mammogram within one year of each other, had Breast Imaging Reporting and Data System (BI-RADS) assessments of normal or benign finding, and no history of breast cancer or surgery. Agreement was assessed of three mammographic techniques (Single-energy X-ray Absorptiometry [SXA], Quantra, and Volpara) with MRI for percent fibroglandular tissue volume, absolute fibroglandular tissue volume, and total breast volume.

Results

Among 99 women, the automated mammographic density techniques were correlated with MRI measures with R² values ranging from 0.40 (log fibroglandular volume) to 0.91 (total breast volume). Substantial agreement measured by kappa statistic was found between all percent fibroglandular tissue measures (0.72 to 0.63), but only moderate agreement for log fibroglandular volumes. The kappa statistics for all percent density measures were highest in the comparisons of the SXA and MRI results. The largest error source between MRI and the mammography techniques was found to be differences in measures of total breast volume.

Conclusion

Automated volumetric fibroglandular tissue measures from screening digital mammograms were in substantial agreement with MRI and if associated with breast cancer could be used in clinical practice to enhance risk assessment and prevention.     

Silicone gel-filled breast implant integrity: a retrospective review of 478 consecutively explanted implants

Concern has been expressed over the long-term integrity of silicone gel breast implants. There are no large series representing experience with these implants outside of the United States. A retrospective case note review of explanted silicone breast implants was performed; 478 implants have been explanted during the past 11 years and relate to the use of these devices since 1971. Loss of implant integrity was not simply related to its age in vivo. Failure was more likely with implants of the late 1970s and early 1980s (second generation) and with subpectoral placement. Implant failure was independent of capsular contracture as the indication for removal (p = 0.09). There is no evidence that the currently used textured silicone gel breast implants are subject to the same loss of integrity as previous examples of these devices. The life span of these implants, the first of which are approaching 10 years in vivo, is at present unknown. Information concerning the integrity of silicone gel breast implants is essential in the current climate for counseling of both new and old implant recipients.     

Camouflage and the Augmentation Mammaplasty

Augmentation mammaplasty has become a safe and accepted surgical procedure since the introduction of silicone prosthesis. Proper selection of the type and size of the implant and careful attention to making the line of incision as nearly invisible as possible are important for a natural-appearing breast. Placement of a silicone gel filled prosthetic implant through a periareolar incision achieves excellent contour and consistency in the augmented breast, with an essentially invisible scar.     

Noninvasive assessment of implant capsules

The assessment of implant capsular contracture has been imprecise and vulnerable to observer bias. Attempts to measure capsules with instruments that measure implant deformability are influenced by surrounding breast tissue, subcutaneous fat, and skin. Xeromammography, B-mode ultrasound, and CT were employed in an effort to provide a noninvasive and accurate method of capsule assessment. Through two study phases, implants were placed bilaterally in a total of 21 rabbits. At 4 months, animals underwent radiologic assessment and were then sacrificed for direct implant capsule measurements. Mammographic measurements, more than ultrasound-derived measurements, strongly correlated with laboratory measures of capsular dimensions and deformability. Cross-table lateral mammographic views were more informative than traditional views, providing measures of diameter and height that both strongly correlated with laboratory measurements. CT is theoretically the most accurate method to assess contracture, but it is impractical because of expense and time requirements. The results indicate that radiologic assessment, in particular by xeromammography, of implant capsules is accurate, practical, and noninvasive. Mammography strongly correlates with laboratory measures of implant capsular contracture and therefore could be used in the clinical setting to assess capsular contracture.     

Breast Tissue Composition and Immunophenotype and Its Relationship with Mammographic Density in Women at High Risk of Breast Cancer

Aim

To investigate the cellular and immunophenotypic basis of mammographic density in women at high risk of breast cancer.

Methods

Mammograms and targeted breast biopsies were accrued from 24 women at high risk of breast cancer. Mammographic density was classified into Wolfe categories and ranked by increasing density. The histological composition and immunophenotypic profile were quantified from digitized haematoxylin and eosin-stained and immunohistochemically-stained (ERα, ERβ, PgR, HER2, Ki-67, and CD31) slides and correlated to mammographic density.

Results

Increasing mammographic density was significantly correlated with increased fibrous stroma proportion (rs (22) = 0.5226, p = 0.0088) and significantly inversely associated with adipose tissue proportion (rs (22) = -0.5409, p = 0.0064). Contrary to previous reports, stromal expression of ERα was common (19/20 cases, 95%). There was significantly higher stromal PgR expression in mammographically-dense breasts (p=0.026).

Conclusions

The proportion of stroma and fat underlies mammographic density in women at high risk of breast cancer. Increased expression of PgR in the stroma of mammographically dense breasts and frequent and unexpected presence of stromal ERα expression raises the possibility that hormone receptor expression in breast stroma may have a role in mediating the effects of exogenous hormonal therapy on mammographic density.     

Evaluation of the effect of silicone breast inserts on X-ray mammography and breast tomosynthesis images: A Monte Carlo simulation study

PurposeBreast augmentation is one of the most popular cosmetic surgeries worldwide. The aim of this study is to investigate the effect of breast implant insertion on the detectability and visibility of lesions on mammography and breast tomosynthesis (BT) images.Materials and methodsThree software phantoms, composed of a homogeneous background with embedded silicone gel structures, and two types of breast abnormalities, microcalcifications (µCs) and masses, were generated. Two X-ray breast imaging modalities were simulated: mammography and BT with six incident monochromatic X-ray beams with energies in the interval between 20 and 30 keV. Projection images were generated using an in-house developed Monte Carlo simulator. The detectability of mammographic findings adjacent to the implant material and the influence of the incident beam energy and implant thickness on the feature detection were studied.ResultsIt was found that implants thicker than 26 mm for the case of mammography and 14 mm for the case of BT obscured the visibility of underlying structures. Although BT demonstrated a lack of contrast, this modality was able to visualize µCs under considerable depths of implant. Increasing the incident beam energy led to better visualization of small µCs, while in the case of breast masses, their detectability was limited.ConclusionsSilicone gel implants introduce a limitation in the image quality of mammograms resulting in low detectability of features. In addition, silicone gel implants obscure partially or totally parts of the image, depending on the size and the thickness of the implant as well the energy of the X-rays used.     

A system for breast implant selection based on patient tissue characteristics and implant-soft tissue dynamics

Primary breast augmentation patients have widely varying characteristics of their breast envelope, parenchyma, and adjacent tissues. When preoperative breast implant selection does not specifically address critical soft-tissue parameters individual to each patient, risks of complications increase. Complications that occur from failure to reconcile a patient's wishes for breast size with her individual tissue characteristics include skin stretch and thinning, ptosis, atrophy of parenchyma, implant edge or shell visibility, implant edge or shell palpability, visible traction rippling, "bottoming" deformities, and lateral implant displacement with widening of the intermammary distance. Previous dimensional systems address implant parenchyma base width relative to implant base width, but no published system adequately addresses or attempts to quantitate the third dimension, tissue stretch, that is critical to estimate amount of fill necessary in a wide range of breast and tissue types. This system addresses the tissue characteristics (T) of the envelope (E), the parenchyma (P), and the implant (I), and the dynamics (D) of implant and filler distribution that affect soft tissues. The acronym TEPID summarizes the key factors that determine aesthetic results and occurrence of problems and reoperations following breast augmentation. This simple, efficient, and clinically practical system focuses on only three tissue measurements to estimate implant volume required to fill each patient's existing breast envelope, on the basis of her individual tissue characteristics: base width of the parenchyma, anterior pull skin stretch, and areola- and/or nipple-to-inframammary-fold distance measured under maximal stretch. The surgeon then adjusts initial volume to address differences in degree of skin stretch (anterior pull skin stretch) and contribution of the patient's existing parenchyma to stretched envelope fill, and to address differences in implant dimensions and filler distribution dynamics. To base decisions of implant pocket location on quantifiable soft-tissue coverage thickness, the system measures soft-tissue pinch thickness of the upper pole and at the inframammary fold. Surgeon time required to measure, estimate, and make preoperative implant selection decisions is less than 5 minutes. This system evolved from compiling and reviewing measurements and results from 330 primary breast augmentations from 1996 to 1999, including round and anatomic implant types with smooth shells and two different textured shells. The TEPID system was then used concurrently with the previous dimensional system for patient tissue evaluation and preoperative implant selection in 627 consecutive primary augmentation cases over a 3-year period from January of 1998 to January of 2001. Implant selection that did not comply with the parameters of the system was necessary in only eight cases. The TEPID system is a simple, efficient, and clinically practical method that allows surgeons to base implant selection on clinically quantifiable, individual patient tissue characteristics.     

Accuracy of touch imprint cytology of image-directed breast core needle biopsies

OBJECTIVE: To evaluate the accuracy of touch imprint (TI) cytology of image-directed core needle biopsy (CNB) specimens of nonpalpable breast lesions. STUDY DESIGN: Fifty-two consecutive CNBs from 44 patients were performed under mammographic or ultrasound guidance. Air- dried TIs of CNBs were stained with Diff-Quik. TI cellularity was considered adequate if six or more ductal cell groups were identified. CNBs and TIs were interpreted in a blinded fashion. RESULTS: TI cellularity was adequate in 37/52 (71%) cases, including 17/20 carcinomas and 20/32 benign lesions. Among 17 carcinomas, TIs were positive in 12, suspicious in 4 and atypical in 1. One case of lactational change was suspicious on TI, and 5/8 fibroadenomas were atypical. No benign lesions were called "carcinoma" on cytology. When lesions categorized as "carcinoma" or "suspicious" were considered positive and those classified as "atypical" or "benign" were scored as negative, TI sensitivity and specificity were 94% and 95%, respectively. When the "atypical" cases were grouped with the positive cases, TI sensitivity was 100%, with 75% specificity. CONCLUSION: With satisfactory cellularity, TIs of CNBs are highly accurate. When immediate evaluation of CNB specimens is important, TIs can potentially decrease the number of biopsy passes required and provide preliminary diagnoses.     

Evidence That Breast Tissue Stiffness Is Associated with Risk of Breast Cancer

Background

Evidence from animal models shows that tissue stiffness increases the invasion and progression of cancers, including mammary cancer. We here use measurements of the volume and the projected area of the compressed breast during mammography to derive estimates of breast tissue stiffness and examine the relationship of stiffness to risk of breast cancer.

Methods

Mammograms were used to measure the volume and projected areas of total and radiologically dense breast tissue in the unaffected breasts of 362 women with newly diagnosed breast cancer (cases) and 656 women of the same age who did not have breast cancer (controls). Measures of breast tissue volume and the projected area of the compressed breast during mammography were used to calculate the deformation of the breast during compression and, with the recorded compression force, to estimate the stiffness of breast tissue. Stiffness was compared in cases and controls, and associations with breast cancer risk examined after adjustment for other risk factors.

Results

After adjustment for percent mammographic density by area measurements, and other risk factors, our estimate of breast tissue stiffness was significantly associated with breast cancer (odds ratio = 1.21, 95% confidence interval = 1.03, 1.43, p = 0.02) and improved breast cancer risk prediction in models with percent mammographic density, by both area and volume measurements.

Conclusion

An estimate of breast tissue stiffness was associated with breast cancer risk and improved risk prediction based on mammographic measures and other risk factors. Stiffness may provide an additional mechanism by which breast tissue composition is associated with risk of breast cancer and merits examination using more direct methods of measurement.     

Frictional contact mechanics methods for soft materials: application to tracking breast cancers

Mammography is currently the most widely used screening and diagnostic tool for breast cancer. Because X-ray images are 2D projections of a 3D object, it is not trivial to localise features identified in mammogram pairs within the breast volume. Furthermore, mammograms represent highly deformed configurations of the breast under compression, thus the tumour localisation process relies on the clinician's experience. Biomechanical models of the breast undergoing mammographic compressions have been developed to overcome this limitation. In this study, we present the development of a modelling framework that implements Coulomb's frictional law with a finite element analysis using a C(1)-continuous Hermite mesh. We compared two methods of this contact mechanics implementation: the penalty method, and the augmented Lagrangian method, the latter of which is more accurate but computationally more expensive compared to the former. Simulation results were compared with experimental data from a soft silicon gel phantom in order to evaluate the modelling accuracy of each method. Both methods resulted in surface-deformation root-mean-square errors of less than 2mm, whilst the maximum internal marker prediction error was less than 3mm when simulating two mammographic-like compressions. Simulation results were confirmed using the augmented Lagrangian method, which provided similar accuracy. We conclude that contact mechanics on soft elastic materials using the penalty method with an appropriate choice of the penalty parameters provides sufficient accuracy (with contact constraints suitably enforced), and may thus be useful for tracking breast tumours between clinical images.     

Altered PTEN expression; a diagnostic marker for differentiating normal, hyperplastic and neoplastic endometrium

Background

Primary non-Hodgkin lymphoma (NHL) of the breast represents 0.04–0.5% of malignant lesions of the breast and accounts for 1.7–2.2% of extra-nodal NHL. Most primary cases are of B-cell phenotype and only rare cases are of T-cell phenotype. Anaplastic large cell lymphoma (ALCL) is a rare T-cell lymphoma typically seen in children and young adults with the breast being one of the least common locations. There are a total of eleven cases of primary ALCL of the breast described in the literature. Eight of these cases occurred in proximity to breast implants, four in relation to silicone breast implant and three in relation to saline filled breast implant with three out of the eight implant related cases having previous history of breast cancer treated surgically. Adjuvant postoperative chemotherapy is given in only one case. Secondary hematological malignancies after breast cancer chemotherapy have been reported in literature. However in contrast to acute myeloid leukemia (AML), the association between lymphoma and administration of chemotherapy has never been clearly demonstrated.

Case Presentation

In this report we present a case of primary ALCL of the breast arising in reconstruction mamoplasty capsule of saline filled breast implant after radical mastectomy for infiltrating ductal carcinoma followed by postoperative chemotherapy twelve years ago.

Conclusion

Primary ALK negative ALCL arising at the site of saline filled breast implant is rare. It is still unclear whether chemotherapy and breast implantation increases risk of secondary hematological malignancies significantly. However, it is important to be aware of these complications and need for careful pathologic examination of tissue removed for implant related complications to make the correct diagnosis for further patient management and treatment. It is important to be aware of this entity at this site as it can be easily misdiagnosed on histologic grounds and to exclude sarcomatoid carcinoma, malignant melanoma and pleomorphic sarcoma by an appropriate panel of immunostains to arrive at the correct diagnosis of ALCL.     

Breast capsulorrhaphy

The malposition of breast prostheses without capsular contracture has become an increasingly frequent event. In our experience with 40 patients over the last 5 years, we have found multiple-layer breast capsulorrhaphy to be a simple, safe, and reliable technique. With this method, repositioning of the breast is easier, more accurate, and more permanent than single-layer closures, which attempt ideal correction of the malpositioned implant on the first try.     

乳腺癌人类表皮生长因子受体2表达与X线表现的相关性分析

目的：对比分析人类表皮生长因子受体2（HER-2）阳性和阴性乳腺癌X线特征,探讨乳腺癌X线征象与HER-2基因之间的相关性。方法：回顾性分析经手术病理确诊的1153例女性乳腺癌患者的X线表现,根据免疫组织化学结果分为HER-2阳性组（314例）和HER-2阴性组（839例）。对比分析两组乳腺癌肿块和钙化的X线特征,肿块主要分析形态、边界及边缘,钙化主要分析形状及分布形式,并对各项分析结果进行X2检验,P〈0.05为差异性有统计学意义。结果：HER-2阳性组乳腺癌较阴性组多表现为钙化（X2=42.528,P=0.001）,HER-2阴性组乳腺癌X线表现多为单纯肿块（389/839,X2=16.374,P=0.001）。星芒状肿块在HER-2阴性组比例较高（57/514,X2=5.912,P=0.015）,两组类圆形（P=0.480）、分叶状（P=0.111）、不规则形肿块（P=0.152）分布比例则无明显统计学差异。HER-2阳性组乳腺癌肿块边界多模糊不清（X2=8.319,P=0.004）,阴性组肿块边界多为部分清楚（X2=5.818,P=0.016）。HER-2阳性组乳腺癌钙化形态多表现为沙砾状（X2=8.955,P=0.001）、多形性和不定形（X2=7.137,P=0.001）,分布形式无明显统计学差异。结论：HER-2阳性乳腺癌X线表现钙化居多,且多为沙砾状、多形性和不定形钙化,肿块边界多模糊不清;HER-2阴性乳腺癌多表现为单纯肿块,边界多为部分清楚,星芒状肿块多见。     

The management of anterior chest wall deformity in patients presenting for breast augmentation

Anterior chest wall asymmetry is sometimes encountered in patients presenting for consideration of breast augmentation. The chest wall asymmetry or deficiency may be significant enough to consider reconstruction at the same time as breast augmentation in a small number of cases. Customized and prefabricated chest wall implants have been used in a variety of conditions including Poland syndrome, pectus excavatum, and sunken anterior chest. Careful moulage preparation and on-table implant modification are needed to "seat" these implants on the skeletal chest wall under the pectoralis major muscle. The chest wall implant provides a base for the subsequent breast prostheses and fills up a bony deficit that cannot be camouflaged by the breast prostheses alone.     

Mammographic Breast Density and Common Genetic Variants in Breast Cancer Risk Prediction

Introduction

Known prediction models for breast cancer can potentially by improved by the addition of mammographic density and common genetic variants identified in genome-wide associations studies known to be associated with risk of the disease. We evaluated the benefit of including mammographic density and the cumulative effect of genetic variants in breast cancer risk prediction among women in a Singapore population.

Methods

We estimated the risk of breast cancer using a prospective cohort of 24,161 women aged 50 to 64 from Singapore with available mammograms and known risk factors for breast cancer who were recruited between 1994 and 1997. We measured mammographic density using the medio-lateral oblique views of both breasts. Each woman’s genotype for 75 SNPs was simulated based on the genotype frequency obtained from the Breast Cancer Association Consortium data and the cumulative effect was summarized by a genetic risk score (GRS). Any improvement in the performance of our proposed prediction model versus one containing only variables from the Gail model was assessed by changes in receiver-operating characteristic and predictive values.

Results

During 17 years of follow-up, 680 breast cancer cases were diagnosed. The multivariate-adjusted hazard ratios (95% confidence intervals) were 1.60 (1.22–2.10), 2.20 (1.65–2.92), 2.33 (1.71–3.20), 2.12 (1.43–3.14), and 3.27 (2.24–4.76) for the corresponding mammographic density categories: 11-20cm², 21-30cm², 31-40cm², 41-50cm², 51-60cm², and 1.10 (1.03–1.16) for GRS. At the predicted absolute 10-year risk thresholds of 2.5% and 3.0%, a model with mammographic density and GRS could correctly identify 0.9% and 0.5% more women who would develop the disease compared to a model using only the Gail variables, respectively.

Conclusion

Mammographic density and common genetic variants can improve the discriminatory power of an established breast cancer risk prediction model among females in Singapore.