- Email: [email protected]
Should we dispense with preoperative breast MRI?
Comment
Levonorgestrel and mifepristone, in an in-vitro model, have different mechanisms of action, because levonorgestrel has no effect on implantation whereas mifepristone can prevent it,9,10 which might also apply to ulipristal. Additionally, in a study in which the date of ovulation was estimated in 625 menstrual cycles in women seeking pregnancy, probability of conception was 0·10 when intercourse occurred 5 days before ovulation and only 6% of the pregnancies could be firmly attributed to spermatozoa that were 3 or more days old.11 This finding suggests that in women receiving ulipristal 72–120 h after an unprotected intercourse, an antiimplantation effect cannot be excluded, as Glasier and colleagues acknowledge. This suggestion has important practical implications at a time when some pro-life physicians and experts begin to accept the fact that levonorgestrel-based emergency contraception does not have abortifacient effects.12,13 Treatment with antiprogestins often simply postpones ovulation and, when this happens, the woman continues to be fertile. In a meta-analysis of 10 mg mifepristone, the relative risk of pregnancy was almost 28 times higher for women reporting unprotected intercourse after treatment, relative to women abstaining from sexual intercourse.14 For this reason, counselling providers should highlight that the risk of pregnancy persists after treatment, because women might falsely think they are protected from pregnancy up to 72–120 h after intercourse. High efficacy, easy access, and an affordable price are crucial for the success of emergency contraception. Today, levonorgestrel is available without prescription in many countries and is not associated with a delay of menses, whereas the availability of mifepristone is highly restricted. Only the future will show whether ulipristal will become easily accessible and affordable for women and whether the slightly higher effectiveness compensates the possible disadvantages involved in postponing ovulation.
*Giuseppe Benagiano, Helena von Hertzen Department of Obstetrics and Gynaecology, Sapienza, University of Rome, 00161 Roma, Italy (GB); and Concept Foundation, Geneva, Switzerland (HvH) [email protected] GB declares that he has no conflicts of interest. HvH declares that one of the aims of the Concept Foundation is to increase access to medical abortion; the Foundation does no work in emergency contraception. 1
2
3
4
5
6
7
8
9
10
11
12 13
14
Glasier AF, Cameron ST, Fine PM, et al. Ulipristal acetate versus levonorgestrel for emergency contraception: a randomised non-inferiority trial and meta-analysis. Lancet 2010; published online Jan 29. DOI:10.1016/ S0140-6736(10)60101-8. von Hertzen H, Piaggio G, Ding J, et al, for the WHO Research Group on Post-ovulatory Methods of Fertility Regulation. Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: a WHO multicentre randomised trial. Lancet 2002; 360: 1803–10. Raymond EG, Trussell J, Polis CB. Population effect of increased access to emergency contraceptive pills: a systematic review. Obstet Gynecol 2007; 109: 181–88. Wilcox AJ, Weinberger CR, Baird DD. Timing of sexual intercourse in relation to ovulation: effects on the probability of conception, survival of the pregnancy, and sex of the baby. N Engl J Med 1995; 333: 1517–21. Poyser NL, Forcelledo ML. A comparison of the pregnancy-terminating potencies of three antiprogestins in guinea-pigs and the effects of sulprostone. Prostaglandins Leukot Essent Fatty Acids 1994; 50: 245–47. Task Force on Postovulatory Methods of Fertility Regulation. Comparison of three single doses of mifepristone as emergency contraception: a randomised trial. Lancet 1999; 353: 697–702. Stratton P, Hartog B, Hajizadeh N, et al. A single mid-follicular dose of CDB-2914, a new antiprogestin, inhibits folliculogenesis and endometrial differentiation in normally cycling women. Hum Reprod 2000; 15: 1092–99. Liu JH, Garzo G, Morris S, Stuenkel C, Ulmann A, Yen SS. Disruption of follicular maturation and delay of ovulation after administration of the antiprogesterone RU486. J Clin Endocrinol Metab 1987; 65: 1135–40. Lalitkumar PG, Lalitkumar S, Meng CX, et al. Mifepristone, but not levonorgestrel, inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model. Hum Reprod 2007; 22: 3031–37. Meng CX, Andersson KL, Bentin-Ley U, Gemzell-Danielsson K, Lalitkumar PG. Effect of levonorgestrel and mifepristone on endometrial receptivity markers in a three-dimensional human endometrial cell culture model. Fertil Steril 2009; 91: 256–64. Wilcox AJ, Baird DD, Dunson DB, McConnaughey DR, Kesner JS, Weinberg CR. On the frequency of intercourse around ovulation; evidence for biological influences. Hum Reprod 2004; 19: 1539–43. Austriaco NPG. Is Plan B Abortifacient? A critical look at the scientific evidence. National Catholic Bioethics Q 2007; 7: 703–07. Hamel R. Thinking ethically about emergency contraception critical judgments require adequate and accurate information. Health Progr 2010; 91: 62–67. Piaggio G, von Hertzen H, Heng Z, Bilian X, Cheng L. Meta-analyses of randomized trials comparing different doses of mifepristone in emergency contraception. Contraception 2003; 68: 447–52.
Should we dispense with preoperative breast MRI? See Articles page 563
528
The COMICE trial, presented in The Lancet today by Lindsay Turnbull and colleagues,1 has been eagerly awaited by the breast cancer community. COMICE is the first randomised trial to assess whether preoperative breast MRI in early-stage breast cancer can decrease reoperation rates. Historically, MRI reveals extent of
disease much better than does conventional imaging,2 and therefore the hope was that MRI information could translate into better surgical outcomes. In COMICE, just over 1600 women with early-stage breast cancer were randomly assigned to receive preoperative MRI or not. The primary endpoint, www.thelancet.com Vol 375 February 13, 2010
reoperation rate (either further wide local excision or mastectomy within 6 months, or a pathological avoidable mastectomy at initial operation) was no different whether MRI was used or not (19% in both groups). Preoperative breast MRI detects more cancer than that seen on conventional imaging—in both the breast with known cancer (16% of women)3 and the contralateral breast (4% of women).4 Because occult cancer can be detected, mastectomies increase by about 8% when MRI is used.3 The initial mastectomy rate in COMICE with MRI was 7%. More mastectomies would seem justified if patients’ outcomes are improved.5 Outcome benefits include decreased recurrence rates and decreased positive margin rates (leading to decreased re-excision rates). Yet, in COMICE, further wide local excision rates were almost the same whether breast MRI was used (10·4%) or not (11·2%), and total reoperation rates were the same (19%). How do we interpret such results? First, re-excision rates at around 10% are extremely low and should be viewed in context of the wider surgical experience. Attempting to remove the smallest volume of tissue possible, our institutional rate is closer to 25%. With the extremely wide negative margins in COMICE, MRI might have little to add in mapping the area of tumour in this population. With smaller resection volumes with higher re-excision rates, the benefit of using MRI might well be greater. Second, COMICE was designed to be pragmatic: modifications in local surgical, pathological or radiological practice were not tracked over the 6-year study at the 45 hospitals with breast cancer multidisciplinary teams. Findings on MRI not linked to any programmatic change in surgical management are likely to yield little, if any, change in patients’ outcome. Moreover, it seems that MRI biopsy or localisation was either not available or not done at all centres after a suspicious MRI finding was identified, because many women had mastectomy without pathological verification of disease (16/58, 27·6% mastectomies in the MRI group). Nowadays, MRI localisation and biopsy equipment is widely available. COMICE spanned 6 years, starting several years before MRI biopsy devices were available. Nevertheless, the high rate of mastectomy without pathological confirmation is troubling and should not happen at sites doing high-quality breast MRI with MRI intervention capability. These pathologically avoidable mastectomies were counted in the reoperation rate, thus diminishing the effect of MRI. www.thelancet.com Vol 375 February 13, 2010
Photolibrary
Comment
Participating centres were defined as large recruiters if one patient per month was enrolled. 86% (1393/1623) of patients were recruited by surgeons who recruited at least ten patients over the 6 years, which meant that a large number (230/1623, 14%) of patients were recruited by surgeons who recruited very few patients: one to two patients per year. Low recruitment might introduce selection bias which could affect the results. Of interest, postmenopausal patients constituted the majority (70%) of patients and therefore might not be the ideal population to benefit from MRI. For invasive lobular carcinoma, COMICE showed that women with this histology were statistically more likely to undergo reoperation. Specialised centres with MRI experience have shown that preoperative MRI can decrease positive margin rates for invasive lobular cancer without increasing mastectomy rates,6 and therefore preoperative staging with MRI in this group might be valid. Breast conservation is a well-established, safe, and effective method of treating breast cancer.7 As patients’ outcomes with breast conservation improve, the possible impact of MRI on women having conservation probably decreases. Yet, MRI images cancer that is not discovered by other imaging methods, and it seems very possible that there are populations for which the routine application of MRI in managing the initial conservative treatment of the ipsilateral breast will be beneficial. For the contralateral breast, COMICE showed a cancer detection rate of 1·6% (13/816), which is slightly below that of other multicentre trials.8 This difference might be due to a real difference in the incidence of contralateral disease in this population or might reflect issues with 529
Comment
quality of imaging and interpretation. Whatever the reason for this difference, a strong argument exists for early detection of contralateral disease, which can lead to simultaneous treatment of synchronous cancers rather than multiple treatments on separate occasions. COMICE does not fully answer whether preoperative breast MRI adds benefit because recurrence and overall survival were not examined. COMICE was designed only to look at reoperation rate. It is a shame that no recurrence data will be obtained. To date there is only one small single-institution retrospective study9 that has examined the question of recurrence; although it found that MRI did not lower recurrence rate, the recurrence rate was exceedingly low in both the MRI (3%) and no MRI groups (4%). A trial as large as COMICE would have the statistical power and potential to examine the possibly more important outcome of recurrence. Because the question of recurrence and overall survival is still unanswered, the complete role of preoperative breast MRI is not yet defined. It is too early to completely dispense with preoperative breast MRI. Importantly, COMICE has shown that preoperative breast MRI might not be for all women and that routine breast MRI in the evaluation of early breast cancer, as managed by those participating in this study, does not decrease reoperation rates. COMICE confirms the difficulty in translating information from images to operating rooms, and raises issues of the impact of breast MRI in settings where surgical excision of the primary tumour is less generous. Future prospective trials will hopefully look at reoperation and/or re-excision, recurrence, and
survival at other high-volume centres with state of the art imaging, biopsy capability, experienced readers, consistent evaluation of pathological margins, and more defined subpopulations of women. Only then can we decide how to select those women who will benefit from preoperative breast MRI. Elizabeth A Morris Department of Radiology, Sloan-Kettering Cancer Center, New York, NY, USA; and Department of Radiology, Weill Cornell Medical College, New York, NY 10065, USA [email protected] I declare that I have no conflicts of interest. 1
2
3
4
5 6
7
8
9
Turnbull L, Brown S, Harvey I, et al. Comparative effectiveness of MRI in breast cancer (COMICE) trial: a randomised controlled trial. Lancet 2010; 375: 563–71. Berg W, Gutierrez L, NessAiver MS, et al. Diagnostic accuracy of mammography, clinical examination, US and MRI imaging in preoperative assessment of breast cancer. Radiology 2004; 233: 830–49. Houssami N, Ciatto S, Macaskill P, et al. Accuracy and surgical impact of magnetic resonance imaging in breast cancer staging: systematic review and meta-analysis in detection of multifocal and multicentric cancer. J Clin Oncol 2008; 26: 3248–58. Brennan ME, Houssami N, Lord S, et al. Accuracy and surgical impact of magnetic resonance imaging in breast cancer staging: systematic review and meta-analysis in detection of multifocal and multicentric cancer. J Clin Oncol 2009; 27: 5640–49. Kuhl C, Kuhn W, Braun M, et al. Pre-operative staging of breast cancer with breast MRI: one step forward, two steps back? Breast 2007; 16: 34–44. Mann RM, Loo CE, Wobbes T, et al. The impact of preoperative breast MRI on the re-excision rate in invasive lobular carcinoma of the breast. Breast Cancer Res Treat 2010; 119: 415–22. Wapnir IL, Anderson SJ, Mamounas EP, et al. Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in five National Surgical Adjuvant Breast and Bowel Project node-positive adjuvant breast cancer trials. J Clin Oncol 2006; 24: 2028–37. Lehman CD, Gatsonis C, Kuhl CK, et al, for the ACRIN Trial 6667 Investigators Group. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med 2007; 356: 1295–303. Solin LJ, Orel SG, Hwang WT, et al. Relationship of breast magnetic resonance imaging to outcome after breast-conservation treatment with radiation for women with early-stage invasive breast carcinoma or ductal carcinoma in situ. J Clin Oncol 2008; 26: 386–91.
Assessing the scale-up of child survival interventions Published Online January 12, 2010 DOI:10.1016/S01406736(09)62193-0 See Editorial page 526 See Articles page 572
530
Two-thirds of the world’s deaths in children younger than 5 years of age could be avoided by the implementation of known technologies.1 Scaling up evidence-based interventions could therefore accelerate reductions in mortality beyond secular trends driven by socioeconomic development.2,3 UNICEF’s large Accelerated Child Survival and Development (ACSD) programme in west Africa set out to scale up evidence-based interventions in 11 countries between 2001 and 2005, spending some US$27 million in the process. Three implementation packages, two preventive and one curative, were
supported through health-facility-based, outreach, and community approaches. In The Lancet today, Jennifer Bryce and colleagues4 present a large careful assessment of the programme in three countries. Using a retrospective design, the investigators found that vertically delivered preventive interventions for expanded immunisation and antenatal care showed improved coverage over time in ACSD focus districts compared with results in comparison areas, whereas health-systemsdependent curative care for children with malaria and pneumonia did not. Mortality decreased over the study www.thelancet.com Vol 375 February 13, 2010
Levonorgestrel and mifepristone, in an in-vitro model, have different mechanisms of action, because levonorgestrel has no effect on implantation whereas mifepristone can prevent it,9,10 which might also apply to ulipristal. Additionally, in a study in which the date of ovulation was estimated in 625 menstrual cycles in women seeking pregnancy, probability of conception was 0·10 when intercourse occurred 5 days before ovulation and only 6% of the pregnancies could be firmly attributed to spermatozoa that were 3 or more days old.11 This finding suggests that in women receiving ulipristal 72–120 h after an unprotected intercourse, an antiimplantation effect cannot be excluded, as Glasier and colleagues acknowledge. This suggestion has important practical implications at a time when some pro-life physicians and experts begin to accept the fact that levonorgestrel-based emergency contraception does not have abortifacient effects.12,13 Treatment with antiprogestins often simply postpones ovulation and, when this happens, the woman continues to be fertile. In a meta-analysis of 10 mg mifepristone, the relative risk of pregnancy was almost 28 times higher for women reporting unprotected intercourse after treatment, relative to women abstaining from sexual intercourse.14 For this reason, counselling providers should highlight that the risk of pregnancy persists after treatment, because women might falsely think they are protected from pregnancy up to 72–120 h after intercourse. High efficacy, easy access, and an affordable price are crucial for the success of emergency contraception. Today, levonorgestrel is available without prescription in many countries and is not associated with a delay of menses, whereas the availability of mifepristone is highly restricted. Only the future will show whether ulipristal will become easily accessible and affordable for women and whether the slightly higher effectiveness compensates the possible disadvantages involved in postponing ovulation.
*Giuseppe Benagiano, Helena von Hertzen Department of Obstetrics and Gynaecology, Sapienza, University of Rome, 00161 Roma, Italy (GB); and Concept Foundation, Geneva, Switzerland (HvH) [email protected] GB declares that he has no conflicts of interest. HvH declares that one of the aims of the Concept Foundation is to increase access to medical abortion; the Foundation does no work in emergency contraception. 1
2
3
4
5
6
7
8
9
10
11
12 13
14
Glasier AF, Cameron ST, Fine PM, et al. Ulipristal acetate versus levonorgestrel for emergency contraception: a randomised non-inferiority trial and meta-analysis. Lancet 2010; published online Jan 29. DOI:10.1016/ S0140-6736(10)60101-8. von Hertzen H, Piaggio G, Ding J, et al, for the WHO Research Group on Post-ovulatory Methods of Fertility Regulation. Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: a WHO multicentre randomised trial. Lancet 2002; 360: 1803–10. Raymond EG, Trussell J, Polis CB. Population effect of increased access to emergency contraceptive pills: a systematic review. Obstet Gynecol 2007; 109: 181–88. Wilcox AJ, Weinberger CR, Baird DD. Timing of sexual intercourse in relation to ovulation: effects on the probability of conception, survival of the pregnancy, and sex of the baby. N Engl J Med 1995; 333: 1517–21. Poyser NL, Forcelledo ML. A comparison of the pregnancy-terminating potencies of three antiprogestins in guinea-pigs and the effects of sulprostone. Prostaglandins Leukot Essent Fatty Acids 1994; 50: 245–47. Task Force on Postovulatory Methods of Fertility Regulation. Comparison of three single doses of mifepristone as emergency contraception: a randomised trial. Lancet 1999; 353: 697–702. Stratton P, Hartog B, Hajizadeh N, et al. A single mid-follicular dose of CDB-2914, a new antiprogestin, inhibits folliculogenesis and endometrial differentiation in normally cycling women. Hum Reprod 2000; 15: 1092–99. Liu JH, Garzo G, Morris S, Stuenkel C, Ulmann A, Yen SS. Disruption of follicular maturation and delay of ovulation after administration of the antiprogesterone RU486. J Clin Endocrinol Metab 1987; 65: 1135–40. Lalitkumar PG, Lalitkumar S, Meng CX, et al. Mifepristone, but not levonorgestrel, inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model. Hum Reprod 2007; 22: 3031–37. Meng CX, Andersson KL, Bentin-Ley U, Gemzell-Danielsson K, Lalitkumar PG. Effect of levonorgestrel and mifepristone on endometrial receptivity markers in a three-dimensional human endometrial cell culture model. Fertil Steril 2009; 91: 256–64. Wilcox AJ, Baird DD, Dunson DB, McConnaughey DR, Kesner JS, Weinberg CR. On the frequency of intercourse around ovulation; evidence for biological influences. Hum Reprod 2004; 19: 1539–43. Austriaco NPG. Is Plan B Abortifacient? A critical look at the scientific evidence. National Catholic Bioethics Q 2007; 7: 703–07. Hamel R. Thinking ethically about emergency contraception critical judgments require adequate and accurate information. Health Progr 2010; 91: 62–67. Piaggio G, von Hertzen H, Heng Z, Bilian X, Cheng L. Meta-analyses of randomized trials comparing different doses of mifepristone in emergency contraception. Contraception 2003; 68: 447–52.
Should we dispense with preoperative breast MRI? See Articles page 563
528
The COMICE trial, presented in The Lancet today by Lindsay Turnbull and colleagues,1 has been eagerly awaited by the breast cancer community. COMICE is the first randomised trial to assess whether preoperative breast MRI in early-stage breast cancer can decrease reoperation rates. Historically, MRI reveals extent of
disease much better than does conventional imaging,2 and therefore the hope was that MRI information could translate into better surgical outcomes. In COMICE, just over 1600 women with early-stage breast cancer were randomly assigned to receive preoperative MRI or not. The primary endpoint, www.thelancet.com Vol 375 February 13, 2010
reoperation rate (either further wide local excision or mastectomy within 6 months, or a pathological avoidable mastectomy at initial operation) was no different whether MRI was used or not (19% in both groups). Preoperative breast MRI detects more cancer than that seen on conventional imaging—in both the breast with known cancer (16% of women)3 and the contralateral breast (4% of women).4 Because occult cancer can be detected, mastectomies increase by about 8% when MRI is used.3 The initial mastectomy rate in COMICE with MRI was 7%. More mastectomies would seem justified if patients’ outcomes are improved.5 Outcome benefits include decreased recurrence rates and decreased positive margin rates (leading to decreased re-excision rates). Yet, in COMICE, further wide local excision rates were almost the same whether breast MRI was used (10·4%) or not (11·2%), and total reoperation rates were the same (19%). How do we interpret such results? First, re-excision rates at around 10% are extremely low and should be viewed in context of the wider surgical experience. Attempting to remove the smallest volume of tissue possible, our institutional rate is closer to 25%. With the extremely wide negative margins in COMICE, MRI might have little to add in mapping the area of tumour in this population. With smaller resection volumes with higher re-excision rates, the benefit of using MRI might well be greater. Second, COMICE was designed to be pragmatic: modifications in local surgical, pathological or radiological practice were not tracked over the 6-year study at the 45 hospitals with breast cancer multidisciplinary teams. Findings on MRI not linked to any programmatic change in surgical management are likely to yield little, if any, change in patients’ outcome. Moreover, it seems that MRI biopsy or localisation was either not available or not done at all centres after a suspicious MRI finding was identified, because many women had mastectomy without pathological verification of disease (16/58, 27·6% mastectomies in the MRI group). Nowadays, MRI localisation and biopsy equipment is widely available. COMICE spanned 6 years, starting several years before MRI biopsy devices were available. Nevertheless, the high rate of mastectomy without pathological confirmation is troubling and should not happen at sites doing high-quality breast MRI with MRI intervention capability. These pathologically avoidable mastectomies were counted in the reoperation rate, thus diminishing the effect of MRI. www.thelancet.com Vol 375 February 13, 2010
Photolibrary
Comment
Participating centres were defined as large recruiters if one patient per month was enrolled. 86% (1393/1623) of patients were recruited by surgeons who recruited at least ten patients over the 6 years, which meant that a large number (230/1623, 14%) of patients were recruited by surgeons who recruited very few patients: one to two patients per year. Low recruitment might introduce selection bias which could affect the results. Of interest, postmenopausal patients constituted the majority (70%) of patients and therefore might not be the ideal population to benefit from MRI. For invasive lobular carcinoma, COMICE showed that women with this histology were statistically more likely to undergo reoperation. Specialised centres with MRI experience have shown that preoperative MRI can decrease positive margin rates for invasive lobular cancer without increasing mastectomy rates,6 and therefore preoperative staging with MRI in this group might be valid. Breast conservation is a well-established, safe, and effective method of treating breast cancer.7 As patients’ outcomes with breast conservation improve, the possible impact of MRI on women having conservation probably decreases. Yet, MRI images cancer that is not discovered by other imaging methods, and it seems very possible that there are populations for which the routine application of MRI in managing the initial conservative treatment of the ipsilateral breast will be beneficial. For the contralateral breast, COMICE showed a cancer detection rate of 1·6% (13/816), which is slightly below that of other multicentre trials.8 This difference might be due to a real difference in the incidence of contralateral disease in this population or might reflect issues with 529
Comment
quality of imaging and interpretation. Whatever the reason for this difference, a strong argument exists for early detection of contralateral disease, which can lead to simultaneous treatment of synchronous cancers rather than multiple treatments on separate occasions. COMICE does not fully answer whether preoperative breast MRI adds benefit because recurrence and overall survival were not examined. COMICE was designed only to look at reoperation rate. It is a shame that no recurrence data will be obtained. To date there is only one small single-institution retrospective study9 that has examined the question of recurrence; although it found that MRI did not lower recurrence rate, the recurrence rate was exceedingly low in both the MRI (3%) and no MRI groups (4%). A trial as large as COMICE would have the statistical power and potential to examine the possibly more important outcome of recurrence. Because the question of recurrence and overall survival is still unanswered, the complete role of preoperative breast MRI is not yet defined. It is too early to completely dispense with preoperative breast MRI. Importantly, COMICE has shown that preoperative breast MRI might not be for all women and that routine breast MRI in the evaluation of early breast cancer, as managed by those participating in this study, does not decrease reoperation rates. COMICE confirms the difficulty in translating information from images to operating rooms, and raises issues of the impact of breast MRI in settings where surgical excision of the primary tumour is less generous. Future prospective trials will hopefully look at reoperation and/or re-excision, recurrence, and
survival at other high-volume centres with state of the art imaging, biopsy capability, experienced readers, consistent evaluation of pathological margins, and more defined subpopulations of women. Only then can we decide how to select those women who will benefit from preoperative breast MRI. Elizabeth A Morris Department of Radiology, Sloan-Kettering Cancer Center, New York, NY, USA; and Department of Radiology, Weill Cornell Medical College, New York, NY 10065, USA [email protected] I declare that I have no conflicts of interest. 1
2
3
4
5 6
7
8
9
Turnbull L, Brown S, Harvey I, et al. Comparative effectiveness of MRI in breast cancer (COMICE) trial: a randomised controlled trial. Lancet 2010; 375: 563–71. Berg W, Gutierrez L, NessAiver MS, et al. Diagnostic accuracy of mammography, clinical examination, US and MRI imaging in preoperative assessment of breast cancer. Radiology 2004; 233: 830–49. Houssami N, Ciatto S, Macaskill P, et al. Accuracy and surgical impact of magnetic resonance imaging in breast cancer staging: systematic review and meta-analysis in detection of multifocal and multicentric cancer. J Clin Oncol 2008; 26: 3248–58. Brennan ME, Houssami N, Lord S, et al. Accuracy and surgical impact of magnetic resonance imaging in breast cancer staging: systematic review and meta-analysis in detection of multifocal and multicentric cancer. J Clin Oncol 2009; 27: 5640–49. Kuhl C, Kuhn W, Braun M, et al. Pre-operative staging of breast cancer with breast MRI: one step forward, two steps back? Breast 2007; 16: 34–44. Mann RM, Loo CE, Wobbes T, et al. The impact of preoperative breast MRI on the re-excision rate in invasive lobular carcinoma of the breast. Breast Cancer Res Treat 2010; 119: 415–22. Wapnir IL, Anderson SJ, Mamounas EP, et al. Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in five National Surgical Adjuvant Breast and Bowel Project node-positive adjuvant breast cancer trials. J Clin Oncol 2006; 24: 2028–37. Lehman CD, Gatsonis C, Kuhl CK, et al, for the ACRIN Trial 6667 Investigators Group. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med 2007; 356: 1295–303. Solin LJ, Orel SG, Hwang WT, et al. Relationship of breast magnetic resonance imaging to outcome after breast-conservation treatment with radiation for women with early-stage invasive breast carcinoma or ductal carcinoma in situ. J Clin Oncol 2008; 26: 386–91.
Assessing the scale-up of child survival interventions Published Online January 12, 2010 DOI:10.1016/S01406736(09)62193-0 See Editorial page 526 See Articles page 572
530
Two-thirds of the world’s deaths in children younger than 5 years of age could be avoided by the implementation of known technologies.1 Scaling up evidence-based interventions could therefore accelerate reductions in mortality beyond secular trends driven by socioeconomic development.2,3 UNICEF’s large Accelerated Child Survival and Development (ACSD) programme in west Africa set out to scale up evidence-based interventions in 11 countries between 2001 and 2005, spending some US$27 million in the process. Three implementation packages, two preventive and one curative, were
supported through health-facility-based, outreach, and community approaches. In The Lancet today, Jennifer Bryce and colleagues4 present a large careful assessment of the programme in three countries. Using a retrospective design, the investigators found that vertically delivered preventive interventions for expanded immunisation and antenatal care showed improved coverage over time in ACSD focus districts compared with results in comparison areas, whereas health-systemsdependent curative care for children with malaria and pneumonia did not. Mortality decreased over the study www.thelancet.com Vol 375 February 13, 2010