The Breast

Editorial Board

2010-02-01

Pre-operative breast MRI in women with recently diagnosed breast cancer – Where to next?

N. Houssami, M. Morrow — 2010-02-01

The appropriate application of breast MRI in the pre-operative evaluation of women with a new diagnosis of breast cancer is currently one of the most debated and controversial issues in breast cancer management. While it initially seemed clear to many that MRI's superior detection capability relative to conventional breast imaging for both the affected breast, and the contralateral breast, would result in improved patient outcomes, an increasing body of evidence based on clinical experience suggests that this may not be the case. This issue of the journal presents some of the varying perspectives on this topic in three commentaries reflecting the views of physicians specializing in breast imaging and the local therapy of breast cancer, and decision-making experts.

Overview of the role of pre-operative breast MRI in the absence of evidence on patient outcomes

Francesco Sardanelli — 2010-02-01

Abstract: The role of pre-operative breast MRI is outlined on the basis of the existing evidence in favor of a superior capability in comparison with mammography and sonography to detect ipsilateral and contralateral malignant lesions and to evaluate the disease extent, including the extensive intraductal component associated with invasive cancers. Patients with a potential higher anticipated benefit from pre-operative MRI can be identified as those: with mammographically dense breasts; with a unilateral multifocal/multicentric cancer or a synchronous bilateral cancer already diagnosed at mammography and sonography; with a lobular invasive cancer; at high-risk for breast cancer; with a cancer which shows a discrepancy in size of >1 cm between mammography and sonography; or under consideration for partial breast irradiation. More limited evidence exists in favor of MRI for evaluating candidates for total skin sparing mastectomy or for patients with Paget's disease. Irrespective of whether the clinical team routinely uses preoperative MRI or not: women newly diagnosed with breast cancer should always be informed of the potential risks and benefits of pre-operative MRI; results of pre-operative MRI should be interpreted taking into account clinical breast examination, mammography, sonography and verified by percutaneous biopsy; MRI-only detected lesions require MR-guidance for needle biopsy and pre-surgical localization, and these should be available or potentially accessible if pre-operative MRI is to be implemented; total therapy delay due to pre-operative MRI (including MRI-induced work-up) should not exceed one month; changes in therapy planning resulting from pre-operative MRI should be decided by a multidisciplinary team.

Counterview: Pre-operative breast MRI (magnetic resonance imaging) is not recommended for all patients with newly diagnosed breast cancer

Lawrence J. Solin — 2010-02-01

Abstract: For the woman with a newly diagnosed early stage breast cancer, the routine use of pre-operative breast MRI (magnetic resonance imaging) is not indicated beyond conventional breast imaging (i.e., mammography with correlation ultrasound as indicated). There is no consistent evidence that a pre-operative breast MRI confers a benefit to the patient by improving clinical outcomes or surgical procedures. In a meta-analysis of studies reporting on the use of pre-operative breast MRI for the patient with an established index cancer, multifocal or multicentric disease was found on breast MRI in 16% of the patients, a rate substantially higher than the rate of local recurrence after breast conserving surgery plus definitive radiation treatment. In the largest retrospective study of patients treated with breast conserving surgery plus radiation, no gain was found for adding a breast MRI to conventional breast imaging. No randomized clinical trial has been designed to evaluate long term clinical outcomes associated with adding a pre-operative breast MRI. Adding pre-operative breast MRI can alter clinical management in ways that are potentially harmful to patients, for example, increased ipsilateral mastectomies, increased contralateral prophylactic mastectomies, increased work-ups, and delay to definitive surgery. In summary, the routine use of pre-operative breast MRI is not warranted for the typical patient with a newly diagnosed early stage breast cancer.

Pre-operative MRI for women with newly diagnosed breast cancer: Perspectives on clinician and patient decision-making when evidence is uncertain

Kirsten J. McCaffery, Jesse Jansen — 2010-02-01

Abstract: The routine use of pre-operative MRI in women with newly diagnosed breast cancer highlights the complexities of the use of new technology when evidence of benefit is uncertain. There are both potential harms and benefits. In the short term patients may desire and feel reassured by further testing and the use of new diagnostic techniques. However, they may also experience greater anxiety and distress from further tests and related follow-up procedures such as biopsy. In the long term MRI may result in more radical treatment decisions which are associated with poorer quality of life for women. Both patients and clinicians often (wrongly) assume that more information via testing leads to better outcomes (information bias). So how should pre-operative MRI be integrated into breast cancer care? First women need to be made aware of the uncertain evidence surrounding MRI. However whether it is appropriate to burden women with complex information and yet another decision at a time of high vulnerability and emotional distress should be considered. One potential solution is to use a Community Informed Consent approach in which a representative sample of patients and healthy women are educated about the benefits and harms and give their informed opinion about whether pre-operative MRI should be offered. Another approach is to provide patients with an evidence based decision aid to support individual informed choice. Either or a combination of both approaches would be acceptable and should be investigated. At present women are poorly informed about pre operative MRI and it is likely that they assume outcomes are be improved as a result. Clear communication about the limits of MRI to patients is needed alongside randomised trials to provide the evidence that benefit indeed outweighs the harms so that all parties involved may be comprehensively informed.

Must we always hunt for a sentinel node?

Oreste Gentilini — 2009-12-14

The introduction of sentinel lymph node biopsy (SLNB) represented a revolution and one of the latest innovations along the path of minimizing the surgical approach towards breast cancer patients. Some of the advantages of this technique, just to mention two, are firstly that SLNB has the same predictive value and allows one to achieve the same information power as axillary lymph node dissection (ALND). Secondly, it is a functional concept rather than an anatomical entity and therefore it can be applied to special clinical scenarios in which lymphatic drainage might be different than it would be under physiologic conditions. In the paper by Tasevski et al. lymphoscintigraphy (LSG) was applied to 18 patients who previously underwent axillary surgery, which in 15 cases was ALND, allowing at least one sentinel node to be identified in 12 patients. In only 3 of 12 patients LSG demonstrated drainage to the ipsilateral axilla only, while the remainder (9 of 12) had drainage to other sites. The authors point out that “the argument that prior axillary surgery or breast radiotherapy will have altered the lymphatic drainage of the breast is a stronger argument for reoperative LSG/SLNB than against. If one believes in the concept of lymphatic mapping, then it is in this setting that it is particularly valuable, identifying drainage to unpredictable locations”. And again the authors state that “preoperative LSG allows the altered lymphatic pathways and sentinel nodes outside the ipsilateral axilla to be identified and biopsied facilitating the surgical staging of the draining regional lymph node”.

Are mastectomy resection margins of clinical relevance? A systematic review

N.P. Rowell — 2009-11-23

Abstract: Although some guidelines support the use of post-mastectomy radiotherapy where the resection margin is involved or close, the scientific basis of this practice is not established. This systematic review explores the relationship between margin status and subsequent relapse.Pooled data from 22 studies (18,863 women) identified an involved post-mastectomy margin in 2.5%, a close margin in 8.0% and muscle or fascia invasion in 7.2% of patients. In a meta-analysis of five studies of non-inflammatory breast cancer without radiotherapy, local recurrence was increased by an involved or close margin (relative risk 2.6; P<0.00001). The effect of muscle or fascia invasion was of borderline significance (relative risk 1.7; P=0.04). In two separate meta-analyses, risk of relapse was related to margin status in women with inflammatory breast cancer (relative risk 3.1; P<0.0001) but not in those undergoing skin-sparing mastectomy (relative risk 2.1; P=0.16).

Translational breast cancer research: Recent advances through the lens of experimental radiotherapy

Jacques Bernier — 2009-11-16

Abstract: Enormous efforts are currently put forth in translational breast cancer research. These efforts are directed to both the development of new drugs and the implementation of novel techniques of local treatment, including radiotherapy. This latter discipline is actually a particularly fertile ground for translational research, since scientists and clinicians are developing novel tools in biology and radiation physics, which reduce the gap between the lab and the clinic, and identify innovative strategies that one didn't even dream, only a few years ago. Nowadays the most recent advances in translational breast cancer research are articulated, in radiation science, around three main domains, namely molecular biology, experimental models for tumour growth and response to treatment, and mechanisms underlying levels of malignant and normal cell radio-sensitivity/radio-resistance. In an attempt to put into perspective what could be the breast cancer radiotherapy of the next decade, these three domains are reviewed and discussed in the present article, at the light of ongoing, “from bench to bedside” studies.

Pre-operative lymphoscintigraphy before sentinel lymph node biopsy for breast cancer

M.A. Mathew, A.K. Saha, T. Saleem, N. Saddozai, I.F. Hutchinson, A. Nejim — 2009-11-13

Abstract: Pre-operative lymphoscintigram for axillary sentinel lymph node biopsy (SLNB) may not be required for successful SLNB. The 117 consecutive patients who underwent SLNB had pre-operative lymphoscintigraphy. The operating surgeon was blinded to the results of the lymphoscintigram before SLNB. After SLNB was complete, the surgeon was unblinded to the results of the lymphoscintigram; re-exploration carried out if more nodes were predicted on the lymphoscintigram. 116 patients (99%) had successful SLNB before unblinding. In 85 patients (73%), operative findings corresponded with scintigraphic findings. In 26 patients (22%), the lymphoscintigram predicted more sentinel nodes than had been found; further nodes were identified and excised in only 4 patients (3%). None were positive for cancer. SLNB was successful in 99% of cases without pre-operative lymphoscintigraphy. Only 3% of patients had further nodes identified as a result of the lymphoscintigram. Pre-operative lymphoscintigraphy does not improve the ability to perform axillary SLNB during breast cancer surgery.

Metronomic administration of pegylated liposomal-doxorubicin in extensively pre-treated metastatic breast cancer patients: A mono-institutional case-series report

2009-11-02

Abstract: Background: Metronomic chemotherapy has shown efficacy in patients with metastatic breast cancer. Pegylated liposomal-doxorubicin (PLD) pharmacokinetic characteristics support the rationale for using the drug in a metronomic fashion, potentially able to combine anthracyclines efficacy to a low toxicity profile.Patients and methods: In a case-series report carried out in both anthracycline-naive and pre-treated metastatic breast cancer patients, we tested feasibility, clinical efficacy and tolerability of PLD administered with a novel metronomic schedule of 20mg/m2 i.v. every two weeks.Results: 52 patients were enrolled and 45 were evaluated. Forty-four patients were assessed for either response or toxicity. Eight patients (18%) had partial responses (PR) and 17 (39%) stable disease (SD), with a clinical benefit (CB) of 45% (95% CI: 30.3%–59.7%). Nineteen patients (43%) had progressive disease (PD). Neither grade 3 nor grade 4 haematological or clinical side effects were recorded, except for 2 patients with grade 3 palmar-plantar erythrodysesthesia (PPE). No cardiac toxicity was recorded.Conclusion: Metronomic administration of PLD is a feasible and active treatment for extensively pre-treated metastatic breast cancer patients, alternative to classic anthracyclines, balancing clinical efficacy with a good quality of life in terms of reduced side effects and low personal costs for the patient.

Worsened oncologic outcomes for women of lower socio-economic status (SES) treated for locally advanced breast cancer (LABC) in Pakistan

Zeba Aziz, Javaid Iqbal, Muhammad Akram, Benjamin O. Anderson — 2009-11-06

Abstract: Two hundred and thirty-seven women, undergoing multimodality treatment for locally advanced breast cancer (LABC), were retrospectively analyzed for age, menopausal status, socio-economic status (SES), tumor size, nodal involvement, tumor grade, estrogen and progesterone receptor (ER, PR) status and tumor stage. Primary purpose was to assess outcomes of these patients treated in a low-income country as defined by the World Bank and using limited-level treatment resources as defined by Breast Health Global Initiative (BHGI) guidelines. Secondary objectives included correlation of predictive and prognostic features with event-free survival (EFS) and overall survival (OS) at 5years.Predictors of decreased EFS or OS included lower SES [P=0.05 (95%CI 0.34–1.0) and P=0.1 (CI 0.29–1.14)], larger tumor size [P=0.01 (95%CI 1.06–1.59) and P=0.3 (CI 0.86–1.50)] and positive lymph node status [P=0.04 (95% CI 1.0–1.55) and P<0.0001 (CI 1.37–2.64).In women diagnosed with LABC in Pakistan, patients with lower SES had larger, more aggressive tumors with worsened survival outcomes. Optimal breast cancer care warrants consideration for health care policies that address access to diagnostic and treatment services for financially disadvantaged women.

Factors contributing to improved local control after mastectomy in patients with breast cancer aged 40 years or younger

2009-11-13

Abstract: Long-term local control rates were studied in a series of 659 patients with invasive breast cancer aged 40 years or younger, who underwent mastectomy in general hospitals in the southern part of the Netherlands between 1988 and 2005. During a median follow-up time of 6.0 years, 34 patients developed a local recurrence in the chest wall without previous or simultaneous evidence of distant disease. The 5- and 10-year actuarial local recurrence rates for the total group were 5.6% (95% confidence interval [95% CI], 3.5–7.7%) and 7.3% (95% CI, 4.7–9.9%), respectively. A multivariate analysis showed that patients receiving radiotherapy (hazards ratio [HR], 0.29; 95% CI, 0.10–0.96) or adjuvant systemic treatment (HR 0.23; 95% CI, 0.08–0.65) had a significantly lower risk of local recurrence. It is concluded that excellent local control rates can be obtained with mastectomy in young women with breast cancer, especially in those who receive adjuvant systemic treatment and/or radiotherapy.

Breast cancer in Latin America: Experts perceptions compared with medical care standards

2009-11-30

Abstract: Background: The BCRF II study presents a systematic review of the norms, recommendations and guidelines that are considered medical care standards (MCS) for breast cancer in 12 Latin American and Caribbean countries. Three key questions from the BCRF I survey data on early detection and diagnosis are presented to identify implementation practice patterns related to MCS.Methods: Information related to MCS was requested from governmental health authorities, cancer institutes, and national scientific and professional societies in 12 Latin American and Caribbean countries. Documents received were reviewed by breast cancer experts from each respective country. Three key survey questions from the BCRF I survey on early detection and diagnosis were reprocessed to provide information related to implementation practice of existing MCS. Results: All countries included in the BCRF II study had medical care standards (MCS) whether published by governmental authorities, national professional or scientific associations, cancer institutes, or adoption of international MCS. Experts reported different practice patterns at a Country level versus a Center level. Overall, 85% of the experts reported that less than 50% of the women with no symptoms undergo a mammography at the Country level compared to 43% at the Center level. For diagnostic suspicion of breast cancer, 80% of experts considered the diagnostic suspicion at a Country level to come from the patient compared to 50% at a Center level. About 30% of patients waited for more than 3 months for a diagnosis at the Country level compared to 7% at the Center level.Conclusion: All the Latin America and Caribbean countries in the study reported the use of similar MCS for breast cancer care. The reported difference between care practiced at a Country level versus a Center level suggests the challenge is not in generating new MCS, but in implementing policies and control mechanisms for compliance with existing MCS, guaranteeing their applicability to all populations.

Breast-conserving surgery in 201 very young patients (<35 years)

2009-11-30

Abstract: Introduction: Surgical treatment of breast cancer in very young patients (<35 years) is still a matter of debate, since age is a predictive factor of local recurrence after breast conservation.Patients and Methods: We retrospectively evaluated outcome and prognostic factors of 201 consecutive patients treated with breast conservation followed by whole breast irradiation between 1997 and 2004 with special attention paid to local control. The average follow up was 72 months (range 13–133 months).Results: The mean age was 32 years (Range 20–34). Invasive ductal carcinoma was found in 175 (87.1%) patients. Two (1%) patients had invasive lobular carcinoma. One-hundred and eighteen patients (58.7%) had tumors of 2 cm or smaller. Sentinel lymph node biopsy was performed in 105 (52.2%) patients. One-hundred and ten (54.7%) patients had node-negative disease, 68 (33.8%) patients had 1–3 positive nodes and 23 (11.4%) +4 positive nodes. Eighteen patients (9.0%) developed a local recurrence, 25 (12.5%) developed distant metastases and 23 patients (11.4%) died during follow up. The 5- and 10-year cumulative incidence of local events were 8.2% and 12,3% respectively. The univariate analysis did not identify any variables affecting local disease-free survival.Conclusions: Breast conservation in very young patients achieves an acceptable local control rate. No prognostic factors were associated with local events.

Breast cancer with non-inflammatory skin involvement: Current data on an underreported entity and its problematic classification

2009-12-17

Abstract: We evaluated 166 breast cancer cases with non-inflammatory skin involvement (NISI), which were classified in the TNM classification as T4b. The distribution of tumour sizes and stages was: ≤3cm:24.1%, 3.1–5cm:21.7%, 5.1–10cm:33.1%, >10cm:21.1%; stages:I/II:21.0%, III:43.4%, IV:35.6%. To assess the impact of NISI on axillary lymph node involvement (ALNI), we analyzed a sub-group of 50 patients with tumours ≤5cm and compared them with a matched control group. NISI was found to be associated with increased ALNI (HR, 2.66; 95%CI, 1.59–4.63; p<0.0001). According to the inherent rules of tumour classification, only tumours with similar morphologic extent and prognostic significance should be combined. Since there is a high grade of heterogeneity, this basic tenet is clearly violated regarding breast cancer with NISI. Our proposal is to eliminate these tumours from the T4 category and to classify them simply by size (T1-3). Due to its prognostic significance, NISI should be indicated by an optional descriptor (e.g. S1).

Sentinel node biopsy in breast cancer: Time has come to systematically perform it before planned axillary clearance

Samir Hidar, Mohamed Bibi, Hédi Khairi — 2009-11-09

Abstract: Sentinel lymph node biopsy is a simple and relatively safe technique that emerged as a standard in the management of early breast cancer. Indications are becoming larger and because this particular node provides significant epidemiological, clinical, pathological, educational and prognostic information efforts must be done to identify it even when a a complete axillary clearance is planned.

Clinical and pathological characteristics of breast cancer patients with history of cesarean delivery

2009-11-13

Antiproliferative effect of the neurohypophyseal peptide oxytocin (OT) in breast cancer cells was previously described in the literature. It was reported that maternal and umbilical plasma OT levels during spontaneous delivery were significantly higher than those at elective cesarean section (c-section). The aim of this study was to investigate clinical and pathological characteristics of breast cancer patients with a history of cesarean delivery and the role of c-section on breast cancer prognosis.