NEWS & VIEWS BREAST CANCER
Why do women opt for contralateral prophylactic mastectomy? Aron Goldhirsch and Shari Gelber
The decision of patients with breast cancer to have contralateral mastectomies is often related to their genetic risk. However, the increasing frequency of this surgical approach is also associated with social and psychological issues such as celebrity experiences and fear of contralateral breast cancer. Appropriate counselling may better inform patients’ surgical choices. Goldhirsch, A. & Gelber, S. Nat. Rev. Clin. Oncol. 11, 443–444 (2014); published online 8 July 2014; doi:10.1038/nrclinonc.2014.116
patients might also be fueled by specialists responding to MRI imaging details, result ing in an increased fear of ‘hidden cancer’, suggested by the higher proportion of CPM in patients who underwent MRI.
‘‘
…drastic surgical solutions have become a socially acceptable and even glamorous approach…
’’
We live in a fascinating period in which information (and misinformation) is avail able with increasing ease, rendering it diffi cult for people to sort out the data that will be truly useful. Whereas reliable reports suggest that breast cancer risk can be reduced by bilateral breast removal5 and by prophy lactic oophorectomy (in young women)6 in women with demonstrated genetic risk for the disease, the chance of reducing risk of breast cancer by surgical means in other circumstances—such as dense breasts or previous radiation to the breast region while treating a malignant lymphoma—has not been proven. Yet, if a curious patient navi gates through websites to find more infor mation regarding her treatment, one of the most popular sites7 will give her the following information: “Preventive mastectomy is a sur gical option for individuals who are at high risk for the development of breast cancer. This preventive operation pertains to women with these characteristics: BRCA1 or BRCA2 mutation carriers (this is the main indica tion for bilateral prophylactic mastectomy); cancer in one breast and a family history of breast cancer; family history of breast cancer (the genetic risk can be passed down through
NATURE REVIEWS | CLINICAL ONCOLOGY
the mother’s or father’s side); radiation ther apy to the chest before the age of 30 (presence of lobular carcinoma in situ); and, finally, having dense breasts or breasts with diffuse microcalcification, as the screening for breast cancer is made difficult. Discussions and decision should be made with the help of spe cialists who can use relevant information and statistical models to predict the individual lifetime risk of development of breast cancer.”7 Some details included in this paragraph have not been substantiated by solid data but yet many patients will take this advice and seri ously discuss the surgical option of CPM with their doctors. It is likely that many of these women will be then ‘talked out’ of having a CPM by their physicians, although no data
Bananastock
Motivated by the increasing rate of contra lateral prophylactic mastectomy (CPM) among women with breast cancer,1 a survey was conducted and recently reported by Sarah T. Hawley et al.2 in JAMA Surgery to better understand the reasons which prompted these women to have CPM. Questionnaires were mailed to 3,133 patients who had been diagnosed with breast cancer, 2,290 (71%) of whom completed baseline forms and 1,536 (68% of the 2,290) completed follow-up surveys approximately 4 years after diagnosis. Ninety-three patients were excluded owing to recurrence, metastases or contralateral breast cancer, which provided 1,447 patients in the analytical sample. CPM was strongly con sidered by 18.9% of the patients in the analy tical sample, and one-third of these patients (7.6%) underwent CPM between years 2005 and 2010. Interestingly, although positive genetic testing (BRCA1 and BRCA2), and strong family history were significant factors associated with receiving CPM, most patients (68.9%) who received CPM versus unilateral surgery had no major genetic or familial risk factors for contralateral disease. Moreover, 20.8% of the patients who underwent CPM had negative genetic test results. Other fea tures positively associated with undergoing CPM were MRI, higher education level and, importantly, greater worry about recurrence. Fear of recurrence was identified as the major non-clinical feature leading to the choice of CPM, confirming findings of similar studies.3,4 The study, conducted in an US urban population, concluded that, in addition to increased genetic or familial risk for bilateral breast cancer, higher level of education and fear of relapse were factors in maximal breast tissue removal. The attitude of the worried
VOLUME 11 | AUGUST 2014 | 443 © 2014 Macmillan Publishers Limited. All rights reserved
NEWS & VIEWS are available about counselling patients with fear of having breast cancer and about the outcome of such counselling. The ease with which plastic surgeons are marketing breast-modifying operations has also changed the attitude of the public towards breast surgery.8 Even health pro fessionals often overestimate cosmetic out comes and underestimate the risks of breast surgery, such as the side effects of surgery itself (pain), cutaneous numbness, etc. 9 The fact that cosmetic surgery of the breast is perceived as an acceptable approach by a large part of the female population may induce women to make the drastic decision to undergo CPM, especially when driven by the fear of cancer reappearance in the contralateral breast. Moreover, drastic surgical solutions have become a socially acceptable and even glam orous approach due to a celebrity’s attitude —the Angelina Jolie effect. Ms Jolie’s state ments have enhanced awareness of health issues related to BRCA mutation carriers, and have also influenced the choice of many women at risk of breast cancer to elect the more extensive surgical approach.10 The fear of cancer recurrence in the con tralateral breast is fueled by the need of many survivors of unilateral breast cancer to undergo regular, generally annually, clinical, laboratory and imaging testing. These patients perceive these tests as a regular traumatic event and little research has been conducted to identify factors that could provide support to women during their follow-up procedures. Such efforts, if identified, might reduce extensive surgical approaches, such as CPM, due to anxiety concerning surveillance procedures. Although CPM might be a reasonable option for women with demonstrated high genetic risk, all women would benefit from assistance in decision making during treatment planning. When pathological characteristics of the tumour and extent of the disease are explained to patients, discus sions regarding genetic risk may aid patients and care givers in deciding whether CPM might be a suitable option. Patients consider ing CPM motivated primarily by fear might also benefit from appropriate counselling. Breast Health Program, European Institute of Oncology, Via G. Ripamonti 435, 20141 Milan, Italy (A.G.). IBCSG Statistical Center, Department of Biostatistics and Computational Biology, Dana–Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA (S.G.). Correspondence to: A.G. [email protected]
444 | AUGUST 2014 | VOLUME 11
Competing interests The authors declare no competing interests. 1.
Pesce, C. E. et al. Changing surgical trends in young patients with early stage breast cancer, 2003 to 2010: a report from the national cancer data base. J. Am. Coll. Surg. 219, 19–28 (2014). 2. Hawley, S. T. et al. Social and clinical determinants of contralateral prophylactic mastectomy. JAMA Surg. 149, 582–589 (2014). 3. Yi, M. et al. Factors affecting the decision of breast cancer patients to undergo contralateral prophylactic mastectomy. Cancer Prev. Res. (Phila.) 3, 1026–1034 (2010). 4. Brewster, A. M. & Parker, P. A. Current knowledge on contralateral prophylactic mastectomy among women with sporadic breast cancer. Oncologist 16, 935–941 (2011). 5. Lostumbo, L., Carbine, N., Wallace, J. & Ezzo, J. Prophylactic mastectomy for the prevention of breast cancer. Cochrane Database Syst. Rev. 4, Art. No.: CD002748 (2004)
http://onlinelibrary.wiley.com/doi/10.1002/ 14651858.CD002748.pub2/abstract. 6. Finch, A. P. et al. Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation. J. Clin. Oncol. 32, 1547–1553 (2014). 7. Preventive mastectomy. Wikipedia.org [online], http://en.wikipedia.org/wiki/ Preventive_mastectomy (2014). 8. Crerand, C. E., Infield, A. L. & Sarwer, D. B. Psychological considerations in cosmetic breast augmentation. Plast. Surg. Nurs. 27, 146–154 (2007). 9. Kling, R. E. et al. The scope of plastic surgery according to 2434 allopathic medical students in the United States. Plast. Reconstr. Surg. 133, 947–956 (2014). 10. Borzekowski, D., Guan, Y., Smith, K. C., Erby, L. H. & Roter, D. L. The Angelina effect: immediate reach, grasp, and impact of going public. Genet. Med. http://dx.doi.org/ 10.1038/gim.2013.181 (2013).
HAEMATOLOGICAL CANCER
The translocation behind follicular lymphoma development Clémentine Sarkozy and Bertrand Coiffier
Healthy individuals carrying the t(14;18) translocation might never develop follicular lymphoma (FL). However, individuals with more than 1 in 10,000 cells carrying this translocation are at high-risk of developing FL. The identification of this high-risk population will help define the pathways driving FL and designing targeted therapies to use before its development. Sarkozy, C. & Coiffier, B. Nat. Rev. Clin. Oncol. 11, 444–445 (2014); published online 17 June 2014; doi:10.1038/nrclinonc.2014.100
Follicular lymphoma (FL) is the second most frequent non-Hodgkin lymphoma (NHL) after diffuse large B‑cell lymphoma, repre senting 20–30% of NHL cases. It is a hetero geneous disease and whereas some patients present with an indolent clinical course with multiple relapses that can span two decades, others have a more-aggressive form with poor survival. FL pathogenesis involves a multi-hit process—including epigenetic reprogramming, acquisition of somatic mutations, and modifications in the microenvironment—in which the genetic hallmark and initiating event of the disease is the t(14;18) tr anslocation that causes BCL2 overexpression.1 Cells bearing the t(14;18) translocation are present in the blood of 50–70% of healthy individuals, indicating that BCL2 over expression is not sufficient for development of FL; in fact, only very few of these individuals will develop the disease.2 In a recent study, Roulland and colleagues3 analysed a cohort of approximately 520,000 healthy participants, and determined that individuals carrying
more than one cell with the t(14;18) trans location per 10,000 blood cells had a 23-fold higher risk of developing FL. Of note, this pre dictive value was accurate regardless of dis ease onset and was still relevant 15 years before FL diagnosis.3 More importantly, the authors showed the clonal relationship between the committed t(14;18) cells in healthy indivi duals and the FL cells, demonstrating the existence of a B‑cell pre‑malignant state in FL.3 The utility of the early detection of this translocation is questionable. In fact, the detection of such cells in healthy indivi duals will likely provoke stress and anxiety. However, the longitudinal follow-up of these patients represents a great opportu nity for the development of epidemiologi cal studies to identify potential roles of the microenvironment in determining FL pro gression. Therefore, the early identifica tion of healthy individuals who will likely develop FL together with the use of power ful biological tools, such as next-generation sequencing, might lead to a different attitude to treat these ‘healthy individuals’. www.nature.com/nrclinonc
© 2014 Macmillan Publishers Limited. All rights reserved
Why do women opt for contralateral prophylactic mastectomy? Aron Goldhirsch and Shari Gelber
The decision of patients with breast cancer to have contralateral mastectomies is often related to their genetic risk. However, the increasing frequency of this surgical approach is also associated with social and psychological issues such as celebrity experiences and fear of contralateral breast cancer. Appropriate counselling may better inform patients’ surgical choices. Goldhirsch, A. & Gelber, S. Nat. Rev. Clin. Oncol. 11, 443–444 (2014); published online 8 July 2014; doi:10.1038/nrclinonc.2014.116
patients might also be fueled by specialists responding to MRI imaging details, result ing in an increased fear of ‘hidden cancer’, suggested by the higher proportion of CPM in patients who underwent MRI.
‘‘
…drastic surgical solutions have become a socially acceptable and even glamorous approach…
’’
We live in a fascinating period in which information (and misinformation) is avail able with increasing ease, rendering it diffi cult for people to sort out the data that will be truly useful. Whereas reliable reports suggest that breast cancer risk can be reduced by bilateral breast removal5 and by prophy lactic oophorectomy (in young women)6 in women with demonstrated genetic risk for the disease, the chance of reducing risk of breast cancer by surgical means in other circumstances—such as dense breasts or previous radiation to the breast region while treating a malignant lymphoma—has not been proven. Yet, if a curious patient navi gates through websites to find more infor mation regarding her treatment, one of the most popular sites7 will give her the following information: “Preventive mastectomy is a sur gical option for individuals who are at high risk for the development of breast cancer. This preventive operation pertains to women with these characteristics: BRCA1 or BRCA2 mutation carriers (this is the main indica tion for bilateral prophylactic mastectomy); cancer in one breast and a family history of breast cancer; family history of breast cancer (the genetic risk can be passed down through
NATURE REVIEWS | CLINICAL ONCOLOGY
the mother’s or father’s side); radiation ther apy to the chest before the age of 30 (presence of lobular carcinoma in situ); and, finally, having dense breasts or breasts with diffuse microcalcification, as the screening for breast cancer is made difficult. Discussions and decision should be made with the help of spe cialists who can use relevant information and statistical models to predict the individual lifetime risk of development of breast cancer.”7 Some details included in this paragraph have not been substantiated by solid data but yet many patients will take this advice and seri ously discuss the surgical option of CPM with their doctors. It is likely that many of these women will be then ‘talked out’ of having a CPM by their physicians, although no data
Bananastock
Motivated by the increasing rate of contra lateral prophylactic mastectomy (CPM) among women with breast cancer,1 a survey was conducted and recently reported by Sarah T. Hawley et al.2 in JAMA Surgery to better understand the reasons which prompted these women to have CPM. Questionnaires were mailed to 3,133 patients who had been diagnosed with breast cancer, 2,290 (71%) of whom completed baseline forms and 1,536 (68% of the 2,290) completed follow-up surveys approximately 4 years after diagnosis. Ninety-three patients were excluded owing to recurrence, metastases or contralateral breast cancer, which provided 1,447 patients in the analytical sample. CPM was strongly con sidered by 18.9% of the patients in the analy tical sample, and one-third of these patients (7.6%) underwent CPM between years 2005 and 2010. Interestingly, although positive genetic testing (BRCA1 and BRCA2), and strong family history were significant factors associated with receiving CPM, most patients (68.9%) who received CPM versus unilateral surgery had no major genetic or familial risk factors for contralateral disease. Moreover, 20.8% of the patients who underwent CPM had negative genetic test results. Other fea tures positively associated with undergoing CPM were MRI, higher education level and, importantly, greater worry about recurrence. Fear of recurrence was identified as the major non-clinical feature leading to the choice of CPM, confirming findings of similar studies.3,4 The study, conducted in an US urban population, concluded that, in addition to increased genetic or familial risk for bilateral breast cancer, higher level of education and fear of relapse were factors in maximal breast tissue removal. The attitude of the worried
VOLUME 11 | AUGUST 2014 | 443 © 2014 Macmillan Publishers Limited. All rights reserved
NEWS & VIEWS are available about counselling patients with fear of having breast cancer and about the outcome of such counselling. The ease with which plastic surgeons are marketing breast-modifying operations has also changed the attitude of the public towards breast surgery.8 Even health pro fessionals often overestimate cosmetic out comes and underestimate the risks of breast surgery, such as the side effects of surgery itself (pain), cutaneous numbness, etc. 9 The fact that cosmetic surgery of the breast is perceived as an acceptable approach by a large part of the female population may induce women to make the drastic decision to undergo CPM, especially when driven by the fear of cancer reappearance in the contralateral breast. Moreover, drastic surgical solutions have become a socially acceptable and even glam orous approach due to a celebrity’s attitude —the Angelina Jolie effect. Ms Jolie’s state ments have enhanced awareness of health issues related to BRCA mutation carriers, and have also influenced the choice of many women at risk of breast cancer to elect the more extensive surgical approach.10 The fear of cancer recurrence in the con tralateral breast is fueled by the need of many survivors of unilateral breast cancer to undergo regular, generally annually, clinical, laboratory and imaging testing. These patients perceive these tests as a regular traumatic event and little research has been conducted to identify factors that could provide support to women during their follow-up procedures. Such efforts, if identified, might reduce extensive surgical approaches, such as CPM, due to anxiety concerning surveillance procedures. Although CPM might be a reasonable option for women with demonstrated high genetic risk, all women would benefit from assistance in decision making during treatment planning. When pathological characteristics of the tumour and extent of the disease are explained to patients, discus sions regarding genetic risk may aid patients and care givers in deciding whether CPM might be a suitable option. Patients consider ing CPM motivated primarily by fear might also benefit from appropriate counselling. Breast Health Program, European Institute of Oncology, Via G. Ripamonti 435, 20141 Milan, Italy (A.G.). IBCSG Statistical Center, Department of Biostatistics and Computational Biology, Dana–Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA (S.G.). Correspondence to: A.G. [email protected]
444 | AUGUST 2014 | VOLUME 11
Competing interests The authors declare no competing interests. 1.
Pesce, C. E. et al. Changing surgical trends in young patients with early stage breast cancer, 2003 to 2010: a report from the national cancer data base. J. Am. Coll. Surg. 219, 19–28 (2014). 2. Hawley, S. T. et al. Social and clinical determinants of contralateral prophylactic mastectomy. JAMA Surg. 149, 582–589 (2014). 3. Yi, M. et al. Factors affecting the decision of breast cancer patients to undergo contralateral prophylactic mastectomy. Cancer Prev. Res. (Phila.) 3, 1026–1034 (2010). 4. Brewster, A. M. & Parker, P. A. Current knowledge on contralateral prophylactic mastectomy among women with sporadic breast cancer. Oncologist 16, 935–941 (2011). 5. Lostumbo, L., Carbine, N., Wallace, J. & Ezzo, J. Prophylactic mastectomy for the prevention of breast cancer. Cochrane Database Syst. Rev. 4, Art. No.: CD002748 (2004)
http://onlinelibrary.wiley.com/doi/10.1002/ 14651858.CD002748.pub2/abstract. 6. Finch, A. P. et al. Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation. J. Clin. Oncol. 32, 1547–1553 (2014). 7. Preventive mastectomy. Wikipedia.org [online], http://en.wikipedia.org/wiki/ Preventive_mastectomy (2014). 8. Crerand, C. E., Infield, A. L. & Sarwer, D. B. Psychological considerations in cosmetic breast augmentation. Plast. Surg. Nurs. 27, 146–154 (2007). 9. Kling, R. E. et al. The scope of plastic surgery according to 2434 allopathic medical students in the United States. Plast. Reconstr. Surg. 133, 947–956 (2014). 10. Borzekowski, D., Guan, Y., Smith, K. C., Erby, L. H. & Roter, D. L. The Angelina effect: immediate reach, grasp, and impact of going public. Genet. Med. http://dx.doi.org/ 10.1038/gim.2013.181 (2013).
HAEMATOLOGICAL CANCER
The translocation behind follicular lymphoma development Clémentine Sarkozy and Bertrand Coiffier
Healthy individuals carrying the t(14;18) translocation might never develop follicular lymphoma (FL). However, individuals with more than 1 in 10,000 cells carrying this translocation are at high-risk of developing FL. The identification of this high-risk population will help define the pathways driving FL and designing targeted therapies to use before its development. Sarkozy, C. & Coiffier, B. Nat. Rev. Clin. Oncol. 11, 444–445 (2014); published online 17 June 2014; doi:10.1038/nrclinonc.2014.100
Follicular lymphoma (FL) is the second most frequent non-Hodgkin lymphoma (NHL) after diffuse large B‑cell lymphoma, repre senting 20–30% of NHL cases. It is a hetero geneous disease and whereas some patients present with an indolent clinical course with multiple relapses that can span two decades, others have a more-aggressive form with poor survival. FL pathogenesis involves a multi-hit process—including epigenetic reprogramming, acquisition of somatic mutations, and modifications in the microenvironment—in which the genetic hallmark and initiating event of the disease is the t(14;18) tr anslocation that causes BCL2 overexpression.1 Cells bearing the t(14;18) translocation are present in the blood of 50–70% of healthy individuals, indicating that BCL2 over expression is not sufficient for development of FL; in fact, only very few of these individuals will develop the disease.2 In a recent study, Roulland and colleagues3 analysed a cohort of approximately 520,000 healthy participants, and determined that individuals carrying
more than one cell with the t(14;18) trans location per 10,000 blood cells had a 23-fold higher risk of developing FL. Of note, this pre dictive value was accurate regardless of dis ease onset and was still relevant 15 years before FL diagnosis.3 More importantly, the authors showed the clonal relationship between the committed t(14;18) cells in healthy indivi duals and the FL cells, demonstrating the existence of a B‑cell pre‑malignant state in FL.3 The utility of the early detection of this translocation is questionable. In fact, the detection of such cells in healthy indivi duals will likely provoke stress and anxiety. However, the longitudinal follow-up of these patients represents a great opportu nity for the development of epidemiologi cal studies to identify potential roles of the microenvironment in determining FL pro gression. Therefore, the early identifica tion of healthy individuals who will likely develop FL together with the use of power ful biological tools, such as next-generation sequencing, might lead to a different attitude to treat these ‘healthy individuals’. www.nature.com/nrclinonc
© 2014 Macmillan Publishers Limited. All rights reserved
