Breast carcinoma in women previously treated for Hodgkin disease: mammographic evaluation.

Although the risk of second malignancies occurring after curative therapy for Hodgkin disease (HD) is well known, few cases of breast carcinoma developing in this setting have been reported. The authors performed a retrospective review of institutional records and identified 27 women with 29 breast carcinomas who had previously undergone treatment of HD and for whom mammograms were available. Two of the 29 carcinomas were synchronous, bilateral tumors. Although the patients' ages ranged from 33 to 75 years, most were young; 16 patients (55%) were younger than 45 years, and nine (31%) were younger than 40 years. Time from treatment for HD to development of breast cancer ranged from 8 to 34 years (mean, 18 years). All women developed ductal carcinoma. Mammography demonstrated 26 of the 29 cancers (90%); 11 of the 29 cancers (38%) were detected only with mammography. In 26 tumors for which clinical findings were known, the results of physical examination were positive in 18 (69%). Women previously treated for HD may be at increased risk of developing breast cancer, which may be bilateral and develop at a young age. This increased risk may be due to scattered radiation to the breast during mantle irradiation. Mammographic screening of these women is indicated. In women who were treated for HD at a young age, routine screening before the age of 35 years is recommended.     

Long-term outcome of breast-conserving therapy for breast cancer

PURPOSE: We present a retrospective analysis of long-term therapeutic results for patients treated in our institution to evaluate the efficacy of breast-conserving therapy (BCT). PATIENTS AND METHODS: The study population was 99 patients (102 breasts) with stage 0, I, and II breast cancer who underwent breast conservation therapy between April 1990 and November 1997. The entire breast was irradiated to a median dose of 50 Gy (range, 50-60 Gy) in 25-30 fractions. An additional 10 Gy in five fractions with 6-12 MeV electrons was given to 23 breasts (23%) with positive surgical margins. RESULTS: The 5-/10-year overall survival, cause-specific survival, relapse-free rate, local recurrence, and regional recurrence rates were 94.6/93.3%, 95.7/94.5%, 88.2/77.5%, 4.2/8.5%, and 2.0/6.3%, respectively. In both uni- and multivariate analyses, age < 40 years was a significant prognostic factor for local recurrence. No severe morbidity was observed. CONCLUSION: The long-term clinical outcome of BCT for early breast carcinoma patients in our department was favorable. Patient age <40 was the most important factor associated with an increased risk of local recurrence in the ipsilateral breast.     

Breast carcinoma in young women previously treated for Hodgkin disease

The increased risk of a second malignant neoplasm developing after treatment for Hodgkin disease is well documented. Subsequent development of breast cancer in women who have been treated for Hodgkin disease is a relatively rare association. To date, no reports of the mammographic detection of breast cancer in this group of women have been published. We report six patients who developed seven breast cancers after treatment for Hodgkin disease. The average age of the women at the time of diagnosis of breast cancer was 33.5 years; diagnosis was made 10-23 years after treatment. There appears to be an increased prevalence of breast carcinoma in women who have been treated for Hodgkin disease. This association should receive further study to evaluate appropriate modifications in routine breast cancer screening for these women.     

131I ablation treatment in young females after the Chernobyl accident.

The Chernobyl accident resulted in a number of cases of thyroid cancer in females under the age of 20 y. Many of these individuals were treated with surgical removal of the thyroid gland followed by 131I ablation of residual thyroid tissue. Epidemiologic evidence demonstrates that 131I treatment for thyroid cancer or hyperthyroidism in adult women confers negligible risk of breast cancer. However, comparable data for younger women do not exist. Studies of external radiation exposure indicate that, for radiation exposures of as low as 0.2-0.7 Gy, the risk of breast cancer is greater for infant and adolescent female breast tissues than for adult female breast tissues. METHODS: The effective half-time of 131I measured in athyrotic patients was used together with the OLINDA/EXM computer code to estimate doses to breast tissue in 10-y-old, 15-y-old, and young adult females from ablation treatment. RESULTS: The dose to pediatric and young adult female breast tissue associated with a 5.6-GBq (150 mCi) ablation treatment may range from 0.35 to 0.55 Gy, resulting in a lifetime risk of breast cancer ranging from 2-4 cases per 100 such individuals exposed and a lifetime risk of solid tumors ranging from 8 to 17 solid tumors per 100 such individuals exposed. Administration of multiple ablation treatments, as often occurs with metastases, could result in doses ranging from 0.7 to 1 Gy, with corresponding increases in the lifetime cancer risk. CONCLUSION: These estimates suggest the need for additional research and a possible need for surveillance of young Chernobyl thyroid cancer patients who received 131I ablation treatment.     

How effective is mammography in detecting breast cancer recurrence in women after Breast Conservation Therapy (BCT) – A systematic literature review

Breast Conservation Therapy (BCT) is now seen as the treatment of choice for early-stage breast cancer, leading to a rising demand for post-operative surveillance. Ongoing mammographic surveillance of the post-operative breast is necessary to minimise the morbidity risk from recurrence. This review evaluates the diagnostic value of mammography following BCT, and identifies the possible challenges with mammography regarding imaging, interpretation and test performance when investigating the treated breast. Relevant literature was reviewed and critically analysed.Three studies reported that surveillance mammography provided a significant survival advantage through early detection of recurrence. Five studies recognised the diagnostic challenges of surveillance mammography following BCT, reporting reduced sensitivity after breast surgery. The need for a more tailored screening strategy after treatment for breast cancer was highlighted in four studies.Although overall mammographic sensitivity is reduced after BCT, it is still proven to be effective in detecting recurrences, therefore remains an important surveillance tool.     

Increased risk of breast cancer following irradiation for Hodgkin's disease is not a result of ATM germline mutations

PURPOSE: Long-term survivors of Hodgkin's disease who received mantle-field irradiation at a young age have a strongly increased risk of developing breast cancer. The purpose of this study was to investigate whether this increased risk was substantially greater among women heterozygous for a germline mutation in the ataxia-telangiectasia gene (ATM). MATERIALS AND METHODS: Thirty-two patients were selected who had developed breast cancer at least 10 years following irradiation for Hodgkin's disease before the age of 45 years. In these patients, the complete open reading frame of the ATM gene was analysed for the presence of germline mutations using the protein truncation test and two mutation-specific tests, followed by genomic sequencing. RESULTS: No A-T disease causing germline mutations were found in these selected Hodgkin patients. However, several alternative splicing events were detected which might influence protein expression levels. CONCLUSIONS: The data suggest that truncating mutations in the ATM gene are not a major component underlying the increased risk of breast cancer following Hodgkin's disease.     

Local Recurrence of Invasive Secretory Breast Carcinoma in a Gravid Patient Post-Mastectomy

This is a case of locally recurrent invasive secretory carcinoma of the breast during pregnancy, detected as a palpable mass in the reconstructed right breast of a 32-year-old female at 24 weeks gestation. The patient was initially diagnosed with secretory carcinoma 8 years prior, for which she underwent nipple sparing mastectomy followed by adjuvant chemotherapy and endocrine therapy. Due to pregnancy, the recurrence was treated initially with conservative excision alone, followed by definitive management postpartum which included wide local excision, sentinel lymph node biopsy and adjuvant chest wall radiation. Secretory carcinoma of the breast is a rare cancer with a predilection for young age and indolent course. This case report describes an unusual case of recurrent secretory carcinoma, of interest due to both its diagnosis during pregnancy, and its recurrence after nipple sparing mastectomy.     

Mucinous carcinoma in an octogenarian: Treatment and management of breast cancer in the elderly

Age is a risk factor for breast cancer in females, and over 60% of female breast cancer deaths occur in those aged 65 and older. As the population in the United States continues to age, it is expected that there will be a commensurate increase in the number of women diagnosed with breast cancer, making understanding of effective treatment and management of breast cancer in the elderly essential.Here, we review the treatment and management of early breast cancer in the elderly. We report a case of invasive mucinous carcinoma in an 80-year-old female detected on routine clinical breast exam by her primary care physician. Mucinous carcinoma of the breast is a type of rare invasive neoplasm that generally carries an excellent prognosis. Following an ultrasound-guided core needle biopsy, a right breast needle localized segmental mastectomy was performed and the patient was prescribed an aromatase inhibitor for hormone-receptor positive tumor. After a follow-up of 8 years, the patient remains free of recurrence or metastasis and vibrantly living meaningful daily life.     

Increased risk of breast cancer following irradiation for Hodgkin‚s disease is not a result of ATM germline mutations

Purpose : Long-term survivors of Hodgkin?s disease who received mantle-field irradiation at a young age have a strongly increased risk of developing breast cancer. The purpose of this study was to investigate whether this increased risk was substantially greater among women heterozygous for a germline mutation in the ataxia-telangiectasia gene (ATM). Materials and methods : Thirty-two patients were selected who had developed breast cancer at least 10 years following irradiation for Hodgkin?s disease before the age of 45 years. In these patients, the complete open reading frame of the ATM gene was analysed for the presence of germline mutations using the protein truncation test and two mutation-specific tests, followed by genomic sequencing. Results : No A-T disease causing germline mutations were found in these selected Hodgkin patients. However, several alternative splicing events were detected which might influence protein expression levels. Conclusions : The data suggest that truncating mutations in the ATM gene are not a major component underlying the increased risk of breast cancer following Hodgkin?s disease.     

Magnetic resonance imaging of the breast: current indications.

Breast magnetic resonance imaging (MRI) plays an increasing role in the management of selected breast cancer patients. MRI is recognized as the most sensitive modality for the detection of invasive breast cancer. Several valuable clinical applications of MRI have emerged for breast cancer detection and diagnosis from clinical investigations. Breast MRI is helpful for women diagnosed with breast cancer who contemplate breast conserving surgery; it provides valuable information on the extent of the disease. MRI can also help assess for residual invasive cancer in patients who have undergone lumpectomy with positive margins at pathology. It is very reliable in differentiating scar tissue from recurrence at the lumpectomy site. MRI is also reliable in finding a breast cancer in women with axillary nodal metastases and unknown primary tumour. MRI can help to monitor the response to chemotherapy. Breast MRI could be a better screening tool than mammography in women with very high risks of developing breast cancer, such as breast cancer gene carriers and patients treated with chest radiation. Other potential uses of MRI include evaluation of the integrity of silicone breast implants and evaluation of the parenchyma in women with silicone gel implants or free injection of silicone gel. However, like any other technique, breast MRI has some drawbacks, including low-to-moderate specificity, high costs, and variability in technique and interpretation. Radiologists must have a clear understanding of valid indications and selection criteria to use this technique appropriately.     

DEGRO practical guidelines: radiotherapy of breast cancer II

Purpose

To complement and update the 2007 practice guidelines of the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO) for radiotherapy (RT) of breast cancer. Owing to its growing clinical relevance, in the current version, a separate paper is dedicated to non-invasive proliferating epithelial neoplasia of the breast. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indication and technique of RT in addition to breast conserving surgery.

Methods

The DEGRO expert panel performed a comprehensive survey of the literature comprising recently published data from clinical controlled trials, systematic reviews as well as meta-analyses, referring to the criteria of evidence-based medicine yielding new aspects compared to 2005 and 2007. The literature search encompassed the period 2008 to September 2012 using databases of PubMed and Guidelines International Network (G-I-N). Search terms were “non invasive breast cancer”, “ductal carcinoma in situ, “dcis”, “borderline breast lesions”, “lobular neoplasia”, “radiotherapy” and “radiation therapy”. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indications of RT and decision making of non-invasive neoplasia of the breast after surgery, especially ductal carcinoma in situ.

Results

Among different non-invasive neoplasia of the breast only the subgroup of pure ductal carcinoma in situ (DCIS; synonym ductal intraepithelial neoplasia, DIN) is considered for further recurrence risk reduction treatment modalities after complete excision of DCIS, particularly RT following breast conserving surgery (BCS), in order to avoid a mastectomy. About half of recurrences are invasive cancers. Up to 50?% of all recurrences require salvage mastectomy. Randomized clinical trials and a huge number of mostly observational studies have unanimously demonstrated that RT significantly reduces recurrence risks of ipsilateral DCIS as well as invasive breast cancer independent of patient age in all subgroups. The recommended total dose is 50 Gy administered as whole breast irradiation (WBI) in single fractions of 1.8 or 2.0 Gy given on 5 days weekly. Retrospective data indicate a possible beneficial effect of an additional tumor bed boost for younger patients. Prospective clinical trials of different dose–volume concepts (hypofractionation, accelerated partial breast irradiation, boost radiotherapy) are still ongoing.

Conclusion

Postoperative radiotherapy permits breast conservation for the majority of women by halving local recurrence as well as reducing progression rates into invasive cancer. New data confirmed this effect in all patient subsets—even in low risk subgroups (LoE 1a).     

Bevölkerungsbezogene Studie über die Anwendung adjuvanter Strahlentherapie bei Patientinnen mit Mammakarzinom

AIM: The assessment of the compliance with consensus recommendations for adjuvant radiation therapy among women with breast cancer. The study is based on data obtained in a population-based cohort-study, which was performed to evaluate the quality of health care for patients with breast cancer. PATIENTS AND METHODS: About one million inhabitants live in the study region Eastern Thuringia, 2,031 cases with invasive breast cancer without distant metastasis (MO) or inflammatory spread were registered from 1995 to 2000. Out of these 1,700 with complete documentation of covariates were included in multivariate analysis. To examine the simultaneous influence of all clinical factors and "caseload" on the likelihood to receive adjuvant radiation therapy a logistic regression model was fitted for radiation therapy after mastectomy. In order to describe the impact of each individual clinic on treatment decision as "caseload" was replaced by the clinics with more than 30 primary treatments. RESULTS: Following breast conserving therapy (BCT) 90.6% of the patients received adjuvant radiation therapy. In the univariate analysis older age was negatively associated with the use of radiation therapy among women with BCT (Table 1). Furthermore, comorbid conditions were negatively associated with the use of radiation therapy. For all other cofactors no associations were found. Subsequent to mastectomy 33.0% of the women underwent radiation therapy (Table 2). Associations between the use of radiation therapy and age, tumor category, number of positive lymph nodes, multiple tumors, histologic differentiation grade, residual tumor as well as hormone receptor status were found. In the multivariate analysis only older age (>/= 70 years) was identified as negative indicator for the utilization of radiation therapy. Among patients with mastectomy increasing tumor size was a positive predictor on radiation therapy (Table 3). In addition more than three positive lymph nodes, multiplicity, poor histologic differentiation grade (G3/4), medial localization, and younger age (35-49 years) were positive predictors for the application of radiation therapy. For R-classification, hormone receptor status and comorbidity no influence on the use of radiation therapy was observed. Among clinics adjusted for case-mix variations in the compliance of treatment recommendation both following BCT and mastectomy were found (Figure 1). CONCLUSION: Following BCT compliance with treatment recommendations regarding radiation therapy was high. Women in older age or with comorbidities received less often radiation therapy. Subsequent to mastectomy indicators for the use of radiation therapy were identified. Among clinics differences in the adherence to treatment recommendations were observed.     

Imaging Surveillance of Patients with Breast Cancer after Primary Treatment: Current Recommendations

Women who have been treated for breast cancer are at risk for second breast cancers, such as ipsilateral recurrence or contralateral metachronous breast cancer. As the number of breast cancer survivors increases, interest in patient management and surveillance after treatment has also increased. However, post-treatment surveillance programs for patients with breast cancer have not been firmly established. In this review, we focus on the imaging modalities that have been used in post-treatment surveillance for patients with breast cancer, such as mammography, ultrasonography, magnetic resonance imaging, and positron emission tomography, the effectiveness of each modality for detecting recurrence, and how they can be applied to manage patients.     

The relationship between microcalcification and in situ carcinoma of the breast

The relationship of microcalcification to lobulo-ductal dysplasia and non-invasive carcinoma was studied in 20 women with in situ carcinoma of the breast. All had microcalcification on the mammogram and in half there was also mammographic evidence of disruption of the breast structure. Three-quarters of the women presented with breast symptoms. Multifocal carcinoma was found in seven patients and the histology suggested that not all foci may progess to extensive duct infiltration or invasion. Calcification was found to occur both in carcinoma and in adjacent benign breast lesions and in three cases no evidence of calcification was found in the carcinoma, but was present in adjacent epitheliosis. The origin and distribution of microcalcification appears to be the same in epithelial hyperplasia, non-invasive carcinoma and invasive carcinoma and there may be a relationship between the amount of calcification and the activity of the epithelial cells. Microcalcification is not specific to breast cancer, but is a product of increased cellular activity in the lobulo-ductal complex and may be extruded into the surrounding interstitial tissue. This implies that microcalcification on the mammogram, particularly if sparse, demonstrates a high risk area of breast rather than a certainty of the presence of carcinoma.     

Breast cancer surveillance in patients treated by radiotherapy for Hodgkin’s lymphoma

Purpose

The authors evaluated the relative risk of developing radiation-induced breast cancer (BC) in women treated with radiotherapy for Hodgkin’s disease (HD) and analysed the imaging features of these breast neoplasms.

Materials and methods

We retrospectively studied 54 women who had all undergone radiotherapy between 1980 and 2010 (median age, 36.6 years). Women aged ≤30 years were screened with clinical breast examination, ultrasound (US) and, if necessary, mammography; women >30 years had clinical breast examination, US and mammography. Three women underwent magnetic resonance (MR) imaging as well.

Results

Mammography detected seven invasive breast cancers in 6/54 women (11.1%). Median age at diagnosis was 26.1 years for HD and 42.4 for breast cancer. Breast cancer was diagnosed following a median latent period from radiotherapy of 15.1 years. Mean radiation dose was 37.6 Gy in women who developed breast cancer and 31.3 Gy in the other women.

Conclusions

In our study, women who were exposed to radiation for HD had a 6.2-fold higher risk of developing breast cancer than the general population. In consideration of the young age and high breast density, women aged ≤30 years should be monitored by US and MR imaging; women aged >30 years should be monitored by US, mammography and, when necessary, MR imaging.     

MR imaging of the skin and nipple of the breast: differentiation between tumour recurrence and post-treatment change

Contrast-enhanced MR imaging of the breast has been found to be valuable in the assessment of local recurrence of previously treated breast cancer. We looked specifically at the appearances of the skin and nipple of the treated breast in order to describe the appearances of post-treatment change and recurrence in this region. Thirty-nine women treated for breast cancer had MR imaging of one or both breasts reviewed retrospectively with particular attention to the nipple and skin. The skin and chest wall were assessed for patients with mastectomies. All available histology of the skin and/or nipple, obtained following MR imaging, was reviewed. In patients who did not undergo surgery following MR imaging, clinical follow-up was obtained. Six of 39 cases had nodular enhancing areas seen on MR imaging, which correlated with histology demonstrating tumour recurrence within the skin and/or nipple. Of the remaining 33 patients, changes of linear or diffuse enhancement were seen in the skin and/or nipple of 15 patients. These changes were shown to be benign post-treatment changes at surgery/biopsy in 4 cases or by clinical follow-up in the remainder. In this article we demonstrate differing patterns of contrast enhancement within the skin and nipple in recurrent breast carcinoma vs. post-treatment changes. This suggests that contrast-enhanced MR imaging of the breast may be a useful tool in differentiating tumour recurrence from post-treatment changes within the skin and nipple.     

The incremental contribution of clinical breast examination to invasive cancer detection in a mammography screening program

OBJECTIVE: The objective of this study was to determine the potential added contribution of clinical breast examination (CBE) to invasive breast cancer detection in a mammography screening program, by categories of age and breast density. SUBJECTS AND METHODS: We prospectively followed 61,688 women aged 40 years or older who had undergone at least one screening examination with mammography and CBE between January 1, 1996, and December 31, 2000, for 1 year after their mammogram for invasive cancer. We computed the incremental sensitivity, specificity, and positive predictive value of CBE over mammography alone for combinations of age and breast density (predominantly fatty or dense). RESULTS: Mammography sensitivity was 78% and combined mammography-CBE sensitivity was 82%, thus CBE detected an additional 4% of invasive cancers. CBE detected a minority of invasive cancers compared with mammography for all age groups and all breast densities. Sensitivity increased from adding CBE to screening mammography for all ages, from 6.8% in women ages 50-59 with dense breasts to 1.8% in women ages 60-69 years with fatty breasts. CBE generally added incrementally more to sensitivity among women with dense breasts. Specificity and positive predictive value declined when CBE was used in conjunction with mammography, and this decrement was more pronounced in women with dense breasts. CONCLUSION: CBE had modest incremental benefit to invasive cancer detection over mammography alone in a screening program, but also led to greater risk of false-positive results. These risks and benefits were greater in women with dense breasts. The balance of risks and benefits must be weighed carefully when evaluating the inclusion of CBE in a screening examination.     

Breast conservation surgery and interstitial brachytherapy in the management of locally recurrent carcinoma of the breast: the Allegheny General Hospital experience

PURPOSE: To evaluate lumpectomy followed by interstitial brachytherapy as an acceptable salvage therapy for women who have developed localized recurrence of breast cancer after conservation surgery and postoperative external radiotherapy. METHODS AND MATERIALS: Between 1/1998 and 10/2006, 21 patients with T0 or T1 in-breast recurrence of carcinoma were offered interstitial low-dose rate brachytherapy after tumor re-excision as an alternative to salvage mastectomy. All patients had failed lumpectomy followed by standard postoperative external beam radiotherapy (range, 5000-6040cGy) as treatment for the initial breast carcinoma. Seven recurred as ductal carcinoma in situ, 2 as infiltrating lobular carcinoma, and 12 as recurrent invasive carcinoma. The recurrent tumors were excised with final margins of resection free of residual disease per National Surgical Adjuvant Breast and Bowel Project definition. Tumor bed implantation was then carried out with an interstitial technique using (192)Ir with the target volume consisting of the tumor bed plus a minimum 1.0-cm clinical margin. The required minimum dose delivered to the target volume was 4500-5000cGy (range, 4500-5530). RESULTS: Twenty of 21 patients were free of local disease with a median observation time of 40 months (range, 3-69). The single patient who developed a second local recurrence was treated successfully with simple mastectomy. Two patients succumbed to systemic disease at 17 and 24 months after salvage implant therapy. One patient developed a contralateral breast cancer. Cosmetic results defined by the National Surgical Adjuvant Breast and Bowel Project cosmesis scale were acceptable. One patient developed a localized seroma requiring multiple needle aspirations before complete resolution. Two patients developed localized skin breakdown in the tumor bed. One healed after 6 months of conservative treatment. The other healed 9 months later with Grade II cosmesis. This patient also developed a concurrent postoperative wound infection. CONCLUSIONS: Repeat lumpectomy followed by brachytherapy is feasible and may be an acceptable alternative to salvage mastectomy in patients who locally fail conservation breast therapy; however, longer followup and greater patient numbers may be needed to better define the role of salvage brachytherapy.     

Comparison of screening CEDM and MRI for women at increased risk for breast cancer: A pilot study

ObjectivesContrast enhanced digital mammography (CEDM) is a new breast imaging technology increasingly used in the diagnostic setting but its utility in the pure screening setting has not been reported. The goal of this pilot study is to prospectively compare screening CEDM to breast MRI in women with an increased risk for breast cancer.MethodsIn this IRB-approved HIPAA-compliant study, 318 women at increased breast cancer risk were consented (December 2012–May 2015) to undergo CEDM in addition to their scheduled MRI. CEDM was performed within 30 days of screening MRI. CEDM was interpreted blinded to MRI. The reference standard was defined as a combination of pathology and 2-year imaging follow-up.ResultsData from 307/318 patients were evaluable. Three cancers (two invasive cancers, one ductal carcinoma in situ) were detected at first round screening: MRI detected all three and CEDM detected the two invasive cancers. None of the three cancers was seen on the low energy mammograms which are comparable to conventional mammography. At 2 year imaging follow up, there were 5 additional screen detected cancers and no palpable cancers. The positive predictive value 3 (PPV₃) for CEDM was 15% (2/13, 95% CI: 2–45%) and 14% for MRI (3/21, 95% CI: 3–36%). The specificity of CEDM and MRI were 94.7% and 94.1% respectively.ConclusionsBoth CEDM and MRI detected additional cancers not seen on conventional mammography, primarily invasive cancers. Our pilot data suggest that CEDM could be valuable as a supplemental imaging exam for women at increased risk for breast cancer who do not meet the criteria for MRI or for whom access to MRI is limited. Validation in larger multi institutional trials is warranted.