14 Ağustos 2008 Perşembe
effect of systemic treatment for advanced breast cancer
While metastatic disease is not curable, treatment can have a beneficial impact on length and quality of life.124 Chemotherapy and endocrine therapy are often effective, and local therapies such as palliative radiotherapy may be very useful.125 Ovarian suppression can be an effective treatment for those younger women with endocrine responsive cancers and retained ovarian function. The LHRH agonist goserelin is effective in suppressing ovarian function in premenopausal women with metastatic breast cancer, and is as beneficial as ovariectomy (oophorectomy) or ovarian irradiation in improving progressionfree and overall survival.126,127 The combination of LHRH agonist and tamoxifen is even more effective in premenopausal women, and significantly prolongs survival compared with LHRH agonist treatment alone.123
differences of Chemotherapy and endocrine therapy in breast cancer
However, it is important to note that the merits of chemotherapy compared with endocrine therapy for younger women are still being assessed. Trials to date have compared chemotherapy alone with endocrine therapy alone. Trials should now be designed to compare chemotherapy followed by tamoxifen with endocrine therapy alone. The current standard of care for women with hormone receptor positive tumours is treatment with both chemotherapy and endocrine therapy; however, some younger women with very good prognosis may decide to have endocrine therapy alone. Trials to determine the impact on disease outcome of chemotherapy plus endocrine therapy are continuing.
differences of Chemotherapy and endocrine therapy in breast cancer
However, it is important to note that the merits of chemotherapy compared with endocrine therapy for younger women are still being assessed. Trials to date have compared chemotherapy alone with endocrine therapy alone. Trials should now be designed to compare chemotherapy followed by tamoxifen with endocrine therapy alone. The current standard of care for women with hormone receptor positive tumours is treatment with both chemotherapy and endocrine therapy; however, some younger women with very good prognosis may decide to have endocrine therapy alone. Trials to determine the impact on disease outcome of chemotherapy plus endocrine therapy are continuing.
endocrine therapy in breast cancer
Combined data from four randomised trials involving 314 women aged less than 35 years indicate that women with hormone receptor positive tumours who did not have endocrine therapy after their chemotherapy had significantly worse disease-free survival than women with hormone receptor negative tumours.15 For premenopausal women with hormone receptor positive cancers, endocrine therapy currently comprises tamoxifen, ovarian suppression or both. Ovarian suppression can be achieved through surgical, radiotherapeutic or chemical means, which should be discussed with the woman as appropriate. Ovarian ablation by surgery or irradiation has been shown to improve long-term survival in women aged younger than 50 years, particularly in the absence of chemotherapy.1 Luteinizing hormone-releasing hormone (LHRH) agonists such as goserelin are effective in suppressing ovarian function chemically; this effect is potentially reversible following cessation of treatment.120 More is known about tamoxifen, which significantly improves recurrence-free and overall survival in women of all age groups and is recommended for most women with oestrogen receptor positive tumours (Level I).116
Treatment with tamoxifen for five years reduces the risk of disease recurrence by up to half in premenopausal women with oestrogen receptor positive cancers.116 This relative reduction in risk will be translated into different absolute benefits depending on individual patient factors.
Ongoing clinical trials are examining whether treatment with tamoxifen for more than five years is beneficial. An average effect of tamoxifen alone in women less than 50 years old would be to improve 10-year disease-free survival from 80% to 85% (small node negative tumour) or from 55% to 65% (small node positive tumour).118 Ovarian suppression may have similar effects. Indeed, in two recently published trials temporary ovarian suppression with goserelin for two years was found to be as effective for disease-free survival as chemotherapy,121 and ovarian
suppression plus tamoxifen was more effective than chemotherapy.122
Treatment with tamoxifen for five years reduces the risk of disease recurrence by up to half in premenopausal women with oestrogen receptor positive cancers.116 This relative reduction in risk will be translated into different absolute benefits depending on individual patient factors.
Ongoing clinical trials are examining whether treatment with tamoxifen for more than five years is beneficial. An average effect of tamoxifen alone in women less than 50 years old would be to improve 10-year disease-free survival from 80% to 85% (small node negative tumour) or from 55% to 65% (small node positive tumour).118 Ovarian suppression may have similar effects. Indeed, in two recently published trials temporary ovarian suppression with goserelin for two years was found to be as effective for disease-free survival as chemotherapy,121 and ovarian
suppression plus tamoxifen was more effective than chemotherapy.122
effect of chemotherapy in breast cancer
Women aged younger than 35 years have a particularly high risk of recurrence and should strongly consider treatment with chemotherapy.117
Clinicians should advise younger women that the benefit of chemotherapy is greater the younger the woman’s age. Chemotherapy will reduce the risk of recurrence by about one-fifth in women aged 60 to 69 years, but by nearly two-fifths in women under the age of 40.
The risk of recurrence never completely goes away. Clinical trials show that women aged younger than 50 years who had chemotherapy have lower rates of recurrence than those who did not, even 10 years after treatment.115 While a younger woman has a potentially long time at risk of recurrence, she also has a long time to accrue the benefit of adjuvant chemotherapy. The risk of recurrence depends on a number of factors, but an average effect of chemotherapy in women less than 50 years old would be to improve 10-year disease-free survival from 80% to 87% (small node negative tumour) or from 55% to 70% (small node positive tumour).118
Clinicians should advise younger women that the benefit of chemotherapy is greater the younger the woman’s age. Chemotherapy will reduce the risk of recurrence by about one-fifth in women aged 60 to 69 years, but by nearly two-fifths in women under the age of 40.
The risk of recurrence never completely goes away. Clinical trials show that women aged younger than 50 years who had chemotherapy have lower rates of recurrence than those who did not, even 10 years after treatment.115 While a younger woman has a potentially long time at risk of recurrence, she also has a long time to accrue the benefit of adjuvant chemotherapy. The risk of recurrence depends on a number of factors, but an average effect of chemotherapy in women less than 50 years old would be to improve 10-year disease-free survival from 80% to 87% (small node negative tumour) or from 55% to 70% (small node positive tumour).118
systemic therapy in breast cancer
Discussions between younger women and clinicians about systemic treatments should include consideration of the individual woman’s underlying risk of recurrence, her treatment preference and the associated toxicities of treatment.
Where there remains a significant risk of distant relapse following local therapy, systemic therapy is frequently given in order to reduce this risk.At present, such adjuvant systemic therapy consists of various cytotoxic chemotherapy regimens and endocrine measures, such as tamoxifen and ovarian suppression. Many clinical trials have been carried out to determine the extent to which giving chemotherapy, or endocrine therapy or both may reduce the risk of recurrence. Five-yearly systematic review and meta-analysis of these trials show that these treatments are effective, although endocrine treatments are only effective where the tumour expresses hormone receptors.1,115,116 The greater the risk of cancer recurrence, the greater the potential benefit from adjuvant therapies. For hormone receptor positive cancers, chemotherapy combined with endocrine therapy is better than either treatment alone.
Where there remains a significant risk of distant relapse following local therapy, systemic therapy is frequently given in order to reduce this risk.At present, such adjuvant systemic therapy consists of various cytotoxic chemotherapy regimens and endocrine measures, such as tamoxifen and ovarian suppression. Many clinical trials have been carried out to determine the extent to which giving chemotherapy, or endocrine therapy or both may reduce the risk of recurrence. Five-yearly systematic review and meta-analysis of these trials show that these treatments are effective, although endocrine treatments are only effective where the tumour expresses hormone receptors.1,115,116 The greater the risk of cancer recurrence, the greater the potential benefit from adjuvant therapies. For hormone receptor positive cancers, chemotherapy combined with endocrine therapy is better than either treatment alone.
psychosocial aspects of local cancer therapy
Younger women appear to experience more concerns about body image,98 greater emotional distress99,100 and poorer adjustment100 following breast surgery than older women.
There is little evidence to suggest a substantial difference in post-operative psychological morbidity according to type of surgery.101 However, some research suggests that younger women experience greater distress following mastectomy than breast conserving surgery.102 Women who undergo breast conserving surgery are also more likely to report better body image than those who have a mastectomy.103 Breast conserving surgery provides an opportunity to preserve the breast shape, facilitates a better fit of clothing, and usually avoids the need for a prosthesis or reconstructive surgery. Evidence that younger women are generally more likely to select breast conserving surgery over mastectomy87,101,104 suggests that concern for body image is an important consideration.
Several studies have reported that, for many young women, fear of cancer and recurrence are prevalent following surgery.50-52 Women may also experience sexual difficulties,105,106 such as a reluctance to resume sexual relations, loss of libido, or feelings of sexual unattractiveness.107
Breast reconstruction
Women report a number of benefits following reconstruction, including more positive body image,108 more positive partner attitudes,109,110 feeling more comfortable without a prosthesis,110 feeling ‘whole’ again, and thinking less about cancer.111,112
There has been little systematic research about age and reconstruction. One exception is a recent study that examined age-related patient satisfaction and psychosocial morbidity following surgery. Among women aged younger than 40 years, those who had breast conserving surgery or reconstruction were less likely to feel sexually unattractive or anxious, and reported more positive body image, than those who had a mastectomy alone.113 In one small randomised trial
involving 64 women aged younger than 60 years,women who received breast reconstruction had lower rates of psychological distress in the short term and improved body image at three and 12 months post-surgery compared with controls.114
There is little evidence to suggest a substantial difference in post-operative psychological morbidity according to type of surgery.101 However, some research suggests that younger women experience greater distress following mastectomy than breast conserving surgery.102 Women who undergo breast conserving surgery are also more likely to report better body image than those who have a mastectomy.103 Breast conserving surgery provides an opportunity to preserve the breast shape, facilitates a better fit of clothing, and usually avoids the need for a prosthesis or reconstructive surgery. Evidence that younger women are generally more likely to select breast conserving surgery over mastectomy87,101,104 suggests that concern for body image is an important consideration.
Several studies have reported that, for many young women, fear of cancer and recurrence are prevalent following surgery.50-52 Women may also experience sexual difficulties,105,106 such as a reluctance to resume sexual relations, loss of libido, or feelings of sexual unattractiveness.107
Breast reconstruction
Women report a number of benefits following reconstruction, including more positive body image,108 more positive partner attitudes,109,110 feeling more comfortable without a prosthesis,110 feeling ‘whole’ again, and thinking less about cancer.111,112
There has been little systematic research about age and reconstruction. One exception is a recent study that examined age-related patient satisfaction and psychosocial morbidity following surgery. Among women aged younger than 40 years, those who had breast conserving surgery or reconstruction were less likely to feel sexually unattractive or anxious, and reported more positive body image, than those who had a mastectomy alone.113 In one small randomised trial
involving 64 women aged younger than 60 years,women who received breast reconstruction had lower rates of psychological distress in the short term and improved body image at three and 12 months post-surgery compared with controls.114
effect of lactation in breast cancer
The effect of radiotherapy on lactation is dose dependent, and the chance of lactating from the irradiated breast after the recommended 50 Gray is likely to be very low. Women who are able to lactate may produce insufficient milk from the treated breast,97 although the contralateral breast is likely to enlarge and sufficient milk may be produced to allow a baby to be fully breastfed. There are no data to make a recommendation about feeding from the treated breast
should milk be produced.
should milk be produced.
Lymphoedema in breast cancer
Following axillary dissection and/or irradiation a woman may experience lymphoedema of the arm. Lymphoedema can occur at any stage, even years after treatment, and can have a significant impact on both physical and psychosocial wellbeing. The predisposing factors to the development of lymphoedema remain poorly understood. Several studies have investigated age
as a risk factor and while some have reported a positive association between lymphoedema risk and older age, others have found no association.95 Lymphoedema may be more prevalent in overweight or obese women, although evidence to support this association is also inconsistent.95 Although sentinel node biopsy has been shown to be an accurate predictor of axillary node metastasis in women with small breast cancer96, the outcomes of clinical trials investigating mortality and morbidity in the long term are unknown. In Australia a clinical trial is currently under way to determine if sentinel node biopsy can avoid the need for axillary dissection in some women and reduce the risk of lymphoedema (Sentinel Node Axillary Clearance [SNAC] trial).
as a risk factor and while some have reported a positive association between lymphoedema risk and older age, others have found no association.95 Lymphoedema may be more prevalent in overweight or obese women, although evidence to support this association is also inconsistent.95 Although sentinel node biopsy has been shown to be an accurate predictor of axillary node metastasis in women with small breast cancer96, the outcomes of clinical trials investigating mortality and morbidity in the long term are unknown. In Australia a clinical trial is currently under way to determine if sentinel node biopsy can avoid the need for axillary dissection in some women and reduce the risk of lymphoedema (Sentinel Node Axillary Clearance [SNAC] trial).
arm morbidity in breast cancer
Arm symptoms may include pain, discomfort, oedema, loss of strength, impaired range of motion and numbness.92 While recent research suggests that younger women are more likely than older women to report experiencing pain93 and numbness of the arm92 following axillary dissection, other studies have reported an association between upper limb pain and older age.94 In one study,women aged younger than 45 years experienced more problems doing household
chores than older women following axillary lymph node dissection.92 Younger women and women who are engaged in paid employment have been shown to report more arm symptoms than older or non-employed women at three and 12 months following axillary dissection.90
chores than older women following axillary lymph node dissection.92 Younger women and women who are engaged in paid employment have been shown to report more arm symptoms than older or non-employed women at three and 12 months following axillary dissection.90
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side effects of local breast cancer therapy
Arm morbidity
There are conflicting results about a relationship between age and arm morbidity following local therapy. Younger women may report more arm symptoms than older women because these symptoms have a greater impact upon their functioning.90,91 It is pertinent for health professionals to ask about arm symptoms and refer women appropriately for treatment.
Lymphoedema
There is no evidence to confirm age as a risk factor in the development of lymphoedema.95
Effect on lactation
It is unlikely that lactation will be possible from the radiotherapy treated breast.
There are conflicting results about a relationship between age and arm morbidity following local therapy. Younger women may report more arm symptoms than older women because these symptoms have a greater impact upon their functioning.90,91 It is pertinent for health professionals to ask about arm symptoms and refer women appropriately for treatment.
Lymphoedema
There is no evidence to confirm age as a risk factor in the development of lymphoedema.95
Effect on lactation
It is unlikely that lactation will be possible from the radiotherapy treated breast.
breast reconstruction in breast cancer
Younger women are more likely than older women to opt for breast reconstruction following mastectomy.58,85-89 Women should be provided with detailed information about immediate and delayed breast reconstruction options before treatment commences so they have the opportunity to consider the procedure adequately and make informed decisions.
A range of options for breast reconstruction are available, and should be explained by relevant members of the multidisciplinary team before any final decisions about surgery and radiotherapy are made. Referral to a plastic surgeon may be appropriate.
A range of options for breast reconstruction are available, and should be explained by relevant members of the multidisciplinary team before any final decisions about surgery and radiotherapy are made. Referral to a plastic surgeon may be appropriate.
timing of breast cancer surgery
For premenopausal women, the effect of timing of surgery in relation to the menstrual cycle is unclear. Evidence suggests that the timing of surgical resection may be relevant to outcome, with a possible advantage to the early luteal phase (approximately days 14 to 20 of the menstrual cycle).83,84 However, this association is inconsistent, and available data are inadequate to provide a recommendation about timing of surgery.
radiotherapy boost in breast cancer
Radiotherapy
Evidence indicates that some of the increases in breast recurrences after conservative treatment are offset by delivering adequate doses of radiotherapy which includes a boost to the tumour bed. Two randomised trials have shown the importance of a radiotherapy boost, particularly in younger women where it has been shown to reduce the local recurrence rate from around 20% to 10% at five years post-treatment.79,80 Optimal systemic therapy is also advised for its additional effect on reducing local recurrence rates
Evidence indicates that some of the increases in breast recurrences after conservative treatment are offset by delivering adequate doses of radiotherapy which includes a boost to the tumour bed. Two randomised trials have shown the importance of a radiotherapy boost, particularly in younger women where it has been shown to reduce the local recurrence rate from around 20% to 10% at five years post-treatment.79,80 Optimal systemic therapy is also advised for its additional effect on reducing local recurrence rates
mastectomy and breast conservation treatment
There are inadequate data about optimal local treatment in the very young, particularly in light of the competing increased systemic risks. Limited evidence suggests that age younger than 35 years is associated with increased risk of recurrence after breast conserving treatment, and also possibly following mastectomy. When discussing options for local therapy, clinicians should offer
information about risk of recurrence based on the woman’s age and disease factors. Ultimately, all treatment decisions should rest with the woman.
Although some conflicting evidence exists,60,61 several studies have reported an independent association between very young age (less than 35 years) andincreases in local recurrence after breast conserving treatment.62-67 Breast cancers in younger women also carry a higher incidence of risk factors implicated in local recurrence, particularly high-grade, vascular invasion and extensive intraductal carcinoma (EIC),64,68-72 although the effect of EIC on local
recurrence has been shown by some to be offset by obtaining clear excision margins.73
Precise recurrence rates are uncertain due to the small numbers of younger women in any of these series, and differences between studies in age categories, tumour stage and grade, length of follow-up time, and statistical methods. Studies suggest the risk of recurrence for young women is approximately 12-30% per cent over a five- to 10-year period.64,68,74-76 Increased risk of recurrence appears to be highest for women under 30 years,67 and rapidly declines over age 35.72 There are similar higher rates of distant relapse in the very young age group.
High-grade tumours and vascular invasion are also implicated in increased risk of local recurrence after mastectomy, making such a choice no real advantage in terms of local control.72 Age younger than 35 years features as a risk factor for local recurrence after mastectomy too, and for some there will be a benefit for post-mastectomy radiotherapy.77 While one analysis has shown a survival advantage for mastectomy over breast conserving treatment for patients less
than 35 years,72 other data have not shown any survival advantage for more radical surgery.64,76,78
information about risk of recurrence based on the woman’s age and disease factors. Ultimately, all treatment decisions should rest with the woman.
Although some conflicting evidence exists,60,61 several studies have reported an independent association between very young age (less than 35 years) andincreases in local recurrence after breast conserving treatment.62-67 Breast cancers in younger women also carry a higher incidence of risk factors implicated in local recurrence, particularly high-grade, vascular invasion and extensive intraductal carcinoma (EIC),64,68-72 although the effect of EIC on local
recurrence has been shown by some to be offset by obtaining clear excision margins.73
Precise recurrence rates are uncertain due to the small numbers of younger women in any of these series, and differences between studies in age categories, tumour stage and grade, length of follow-up time, and statistical methods. Studies suggest the risk of recurrence for young women is approximately 12-30% per cent over a five- to 10-year period.64,68,74-76 Increased risk of recurrence appears to be highest for women under 30 years,67 and rapidly declines over age 35.72 There are similar higher rates of distant relapse in the very young age group.
High-grade tumours and vascular invasion are also implicated in increased risk of local recurrence after mastectomy, making such a choice no real advantage in terms of local control.72 Age younger than 35 years features as a risk factor for local recurrence after mastectomy too, and for some there will be a benefit for post-mastectomy radiotherapy.77 While one analysis has shown a survival advantage for mastectomy over breast conserving treatment for patients less
than 35 years,72 other data have not shown any survival advantage for more radical surgery.64,76,78
local therapy of breast cancer
There have been no randomised trials designed to determine whether younger women are at increased risk of local recurrence following breast surgery compared with their older counterparts. Disease outcomes for younger women have primarily been determined by analysing data for those younger women who have participated in large trials examining risk factors for recurrence. The number of young women in these studies has been relatively small, and the comparison of results across studies has been impeded by the use of differing age classifications.
clinical trials in breast cancer
Australian research indicates that younger women are more likely than older women to be informed about, and offered the opportunity to participate in, clinical trials.58
Clinical trials are an essential component of the process of finding better treatments for breast cancer, and it is appropriate for clinicians to discuss participation in clinical trials with women. Evidence suggests that women who participate in clinical trials have better survival outcomes than women given similar treatment outside trials (Level III).59 A high participation rate will enable outstanding research questions to be answered more quickly. Information about trials for which younger women may be eligible is available from the Australian New Zealand Breast Cancer Trials Group (www.anzbctg.org) and the NHMRC Clinical Trials Centre (www.ctc.usyd.edu.au).
Clinical trials are an essential component of the process of finding better treatments for breast cancer, and it is appropriate for clinicians to discuss participation in clinical trials with women. Evidence suggests that women who participate in clinical trials have better survival outcomes than women given similar treatment outside trials (Level III).59 A high participation rate will enable outstanding research questions to be answered more quickly. Information about trials for which younger women may be eligible is available from the Australian New Zealand Breast Cancer Trials Group (www.anzbctg.org) and the NHMRC Clinical Trials Centre (www.ctc.usyd.edu.au).
multidisciplinary care in breast cancer
A multidisciplinary approach provides optimal therapy for all women with breast cancer. The disciplines represented by the core team should minimally include surgery, radiation and medical oncology, pathology, radiology and supportive care; the woman’s general practitioner should also be part of the team. In treating younger women, the team may be expanded to include other health professionals such as a plastic surgeon, fertility expert, psychologist and/or
psychiatrist.
Survival outcomes for patients with breast and other cancers are better if they are treated by a clinician who has access to the full range of treatment options in a multidisciplinary setting (Level III).57 As for older women, the surgeon is usually the specialist clinician of first contact in the management of a younger woman with breast cancer. The need for a younger woman to have preoperative consultations with a radiation oncologist and/or a medical oncologist will depend on the planning discussions held by the multidisciplinary team. Preoperative consultation with a radiation oncologist should be considered if radiotherapy is thought to be likely.
The timing of a consultation between a younger woman and a medical oncologist should be assessed on a case-by-case basis. It is pertinent for health professionals to consider pre-operative consultation with a medical oncologist and/or gynaecologist if a woman is concerned about fertility issues (see Section 7 for more information about infertility following treatment). However, as the need for systemic therapy is usually determined by the histology of the tumour
and regional lymph nodes, it may be reasonable to involve a medical oncologist in treatment planning at a later stage.
It is pertinent for members of the multidisciplinary team to inform younger women about support services specifically catering to their needs, such as younger women’s support groups. Individual women will require a varying degree of support, ranging from practical advice about obtaining breast prostheses after mastectomy to professional counselling if they are emotionally
or psychologically distressed.
psychiatrist.
Survival outcomes for patients with breast and other cancers are better if they are treated by a clinician who has access to the full range of treatment options in a multidisciplinary setting (Level III).57 As for older women, the surgeon is usually the specialist clinician of first contact in the management of a younger woman with breast cancer. The need for a younger woman to have preoperative consultations with a radiation oncologist and/or a medical oncologist will depend on the planning discussions held by the multidisciplinary team. Preoperative consultation with a radiation oncologist should be considered if radiotherapy is thought to be likely.
The timing of a consultation between a younger woman and a medical oncologist should be assessed on a case-by-case basis. It is pertinent for health professionals to consider pre-operative consultation with a medical oncologist and/or gynaecologist if a woman is concerned about fertility issues (see Section 7 for more information about infertility following treatment). However, as the need for systemic therapy is usually determined by the histology of the tumour
and regional lymph nodes, it may be reasonable to involve a medical oncologist in treatment planning at a later stage.
It is pertinent for members of the multidisciplinary team to inform younger women about support services specifically catering to their needs, such as younger women’s support groups. Individual women will require a varying degree of support, ranging from practical advice about obtaining breast prostheses after mastectomy to professional counselling if they are emotionally
or psychologically distressed.
genetic testing after cancer diagnosis
Following a diagnosis of breast cancer, some younger women may be concerned about the risk of breast cancer developing in their close family members, such as their mother, sisters or daughters. It is important for these women to discuss their concerns with a health professional, who may recommend referral to a specialist family cancer clinic if appropriate.
Family cancer clinics provide a service for people with a family history of cancer and their health professionals and can give an estimate of the likelihood of a woman carrying an inherited mutation in a cancer predisposing gene. Although it is now technically possible to test for mutations in some cancer predisposing genes, genetic testing is an appropriate option for only a small proportion of individuals, usually those with a strong family history of breast and/or ovarian cancer.
Genetic testing is offered only with pre- and post-test counselling to discuss the limitations of testing, plus the advantages and disadvantages of being tested, both for the woman and her family. Should a mutation be found, predictive genetic testing may be offered to unaffected adult family members (both male and female) who may also be at risk of carrying the same mutation. Women who test positive for a mutation in BRCA1 or BRCA2 are also at increased risk of developing a second primary breast cancer or ovarian cancer, and should be referred to a cancer specialist for discussion about management options.
Family cancer clinics provide a service for people with a family history of cancer and their health professionals and can give an estimate of the likelihood of a woman carrying an inherited mutation in a cancer predisposing gene. Although it is now technically possible to test for mutations in some cancer predisposing genes, genetic testing is an appropriate option for only a small proportion of individuals, usually those with a strong family history of breast and/or ovarian cancer.
Genetic testing is offered only with pre- and post-test counselling to discuss the limitations of testing, plus the advantages and disadvantages of being tested, both for the woman and her family. Should a mutation be found, predictive genetic testing may be offered to unaffected adult family members (both male and female) who may also be at risk of carrying the same mutation. Women who test positive for a mutation in BRCA1 or BRCA2 are also at increased risk of developing a second primary breast cancer or ovarian cancer, and should be referred to a cancer specialist for discussion about management options.
treatment preferences in breast cancer
Many younger women prefer active involvement in treatment decision making; this is particularly the case for women with a higher level of education.49 Clinicians should offer detailed information about treatment options and seek women’s preferences.
A diagnosis of breast cancer prompts concerns about the future and survival, and fear of death and dying.50-52 Consideration of the needs of children and family is important for young women, and there is some evidence to suggest that women with dependants may be more willing to assume risks in treatments for even small potential increases in life expectancy.53 Other important issues of concern may include fertility,54 body image,55,56 career and finances.47 These issues should be identified and addressed by clinicians when providing information and discussing treatment options.
Women appear more likely to perceive greater participation in and control over decision making when clinicians encourage and facilitate their involvement.49
A diagnosis of breast cancer prompts concerns about the future and survival, and fear of death and dying.50-52 Consideration of the needs of children and family is important for young women, and there is some evidence to suggest that women with dependants may be more willing to assume risks in treatments for even small potential increases in life expectancy.53 Other important issues of concern may include fertility,54 body image,55,56 career and finances.47 These issues should be identified and addressed by clinicians when providing information and discussing treatment options.
Women appear more likely to perceive greater participation in and control over decision making when clinicians encourage and facilitate their involvement.49
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psycholigical impact of breast cancer diagnosis
Younger women appear to experience greater emotional distress than older women when diagnosed with primary breast cancer.44
Traumatic imagery, such as intrusive thoughts about breast cancer, is more common in younger women.45 Issues of particular concern to younger women include shock and distress at the untimeliness of the diagnosis, a sense of being different and isolated, guilt about the impact on partners, concerns for children,46 and a sense of being a different person with different priorities.47 Limited evidence suggests that younger women will also experience greater emotional distress when diagnosed with a recurrence,48 as this raises fear about the future and the possibility of dying.
Traumatic imagery, such as intrusive thoughts about breast cancer, is more common in younger women.45 Issues of particular concern to younger women include shock and distress at the untimeliness of the diagnosis, a sense of being different and isolated, guilt about the impact on partners, concerns for children,46 and a sense of being a different person with different priorities.47 Limited evidence suggests that younger women will also experience greater emotional distress when diagnosed with a recurrence,48 as this raises fear about the future and the possibility of dying.
detection and diagnosis of breast cancer
As the sensitivity for mammography is lower at younger ages, ultrasound examination is recommended as the first-line imaging test for symptomatic women younger than 35 years and for women who are pregnant or lactating; however, both imaging modalities may be used as part of the triple test to provide complementary information.42
Most breast cancers in younger women are diagnosed as a result of the investigation of a lump or other breast symptom;35 these symptoms are most often self- or partner-detected.36,37 While some younger women may delay in presenting with breast symptoms, evidence suggests that physician delay in referral for assessment is a key factor in delaying diagnosis.34,38,39 A systematic review of five studies about delayed presentation of symptomatic breast cancer
reported an association between younger age and physician delay in referral in four studies involving a total of 5,146 women.40 This may be attributable to the belief that a woman is ‘too young to have breast cancer’, as incidence in this population is low and breast changes in young women are common. It is recommended that the triple test approach is used in investigating breast symptoms. The components of the triple test are clinical breast examination and
medical history; breast imaging (mammography, ultrasound, or both); and nonexcision biopsy (fine needle aspiration biopsy, core biopsy, or both).41 While the correct sequencing of tests is important to the overall interpretation of the results, not all breast symptoms will require investigation using all three tests.
Most breast symptoms are physiological and are adequately assessed by thorough clinical breast examination with or without imaging.
If there is any suspicion of cancer on clinical examination or ultrasound, a mammogram should be performed and, in many instances, ultrasound and mammography are both used to provide complementary information. Any clinical or imaging abnormality should be further investigated with percutaneous biopsy tests.
Most breast cancers in younger women are diagnosed as a result of the investigation of a lump or other breast symptom;35 these symptoms are most often self- or partner-detected.36,37 While some younger women may delay in presenting with breast symptoms, evidence suggests that physician delay in referral for assessment is a key factor in delaying diagnosis.34,38,39 A systematic review of five studies about delayed presentation of symptomatic breast cancer
reported an association between younger age and physician delay in referral in four studies involving a total of 5,146 women.40 This may be attributable to the belief that a woman is ‘too young to have breast cancer’, as incidence in this population is low and breast changes in young women are common. It is recommended that the triple test approach is used in investigating breast symptoms. The components of the triple test are clinical breast examination and
medical history; breast imaging (mammography, ultrasound, or both); and nonexcision biopsy (fine needle aspiration biopsy, core biopsy, or both).41 While the correct sequencing of tests is important to the overall interpretation of the results, not all breast symptoms will require investigation using all three tests.
Most breast symptoms are physiological and are adequately assessed by thorough clinical breast examination with or without imaging.
If there is any suspicion of cancer on clinical examination or ultrasound, a mammogram should be performed and, in many instances, ultrasound and mammography are both used to provide complementary information. Any clinical or imaging abnormality should be further investigated with percutaneous biopsy tests.
family history of breast cancer
If a woman with a family history of breast cancer wishes to clarify her genetic risk or that of her family, health professionals should discuss referral to specialist genetic services for advice, appropriate counselling and management. For more information, refer to Advice about familial aspects of breast cancer and ovarian cancer:A guide for health professionals.28
A history of breast and/or ovarian cancer in one or more first-degree relatives may be the strongest risk factor for younger women,23 particularly if the affected relative was younger than 50 years at diagnosis.27 In one Australian case-control study of women aged younger than 40, 12% of women with breast cancer compared with 5% of controls reported a history of the disease in a first-degree relative of any age.23 Family history taking should include both the maternal and paternal sides of a family.
Several genes are associated with a high risk of breast or ovarian cancer. It is estimated that between 1% and 5% of all breast and ovarian cancers involve the inheritance of a mutated gene.28 In younger women, the proportion of breast and ovarian cancers believed to involve an inherited mutated gene is higher.29 International data from samples of women not selected for family history suggest the prevalence of a BRCA1 mutation in women diagnosed with breast
cancer before age 35 is approximately 6-11%.29-31
In some circumstances,women with a very strong family history, or who are found by genetic testing to have inherited a mutated copy of a high-risk gene, may wish to explore possibilities for reducing their risk of developing breast cancer, such as prophylactic mastectomy and/or prophylactic bilateral salpingooophorectomy. Women who are at significantly increased risk of developing breast cancer should be referred for appropriate counselling before any therapeutic decisions are made.
Women with a family history of breast cancer may experience significant levels of distress. One study of women who had one or more first-degree relatives with breast cancer found that 27% of these women had a level of psychological distress consistent with the need for counselling.32 The Psychosocial clinical practice guidelines provide examples of questions health professionals can use to screen women who may be experiencing psychological distress.33
A history of breast and/or ovarian cancer in one or more first-degree relatives may be the strongest risk factor for younger women,23 particularly if the affected relative was younger than 50 years at diagnosis.27 In one Australian case-control study of women aged younger than 40, 12% of women with breast cancer compared with 5% of controls reported a history of the disease in a first-degree relative of any age.23 Family history taking should include both the maternal and paternal sides of a family.
Several genes are associated with a high risk of breast or ovarian cancer. It is estimated that between 1% and 5% of all breast and ovarian cancers involve the inheritance of a mutated gene.28 In younger women, the proportion of breast and ovarian cancers believed to involve an inherited mutated gene is higher.29 International data from samples of women not selected for family history suggest the prevalence of a BRCA1 mutation in women diagnosed with breast
cancer before age 35 is approximately 6-11%.29-31
In some circumstances,women with a very strong family history, or who are found by genetic testing to have inherited a mutated copy of a high-risk gene, may wish to explore possibilities for reducing their risk of developing breast cancer, such as prophylactic mastectomy and/or prophylactic bilateral salpingooophorectomy. Women who are at significantly increased risk of developing breast cancer should be referred for appropriate counselling before any therapeutic decisions are made.
Women with a family history of breast cancer may experience significant levels of distress. One study of women who had one or more first-degree relatives with breast cancer found that 27% of these women had a level of psychological distress consistent with the need for counselling.32 The Psychosocial clinical practice guidelines provide examples of questions health professionals can use to screen women who may be experiencing psychological distress.33
prediagnosis of breast cancer
The causes of breast cancer are not fully understood. Ageing, genetic factors and environmental influences all appear to play a part,22 although the effects of some of these risk factors may be different for younger and older women.23,24 For younger women, a strong family history of breast cancer is one of the most important risk factors.23 However, most young women who develop breast cancer do not have a family history of the disease.
Other factors that may be associated with increased breast cancer risk for younger women include: a history of proliferative benign breast disease; nulliparity, low parity, or late age at first full-term pregnancy; and short duration of breastfeeding or never having lactated.24 Current or recent use of combined oral contraceptives is associated with a slightly increased risk of breast cancer, but there is no evidence of excess breast cancer risk 10 or more years after cessation of oral contraceptive use.25 A link between induced abortion and breast cancer risk has been hypothesised, but the results of a large, populationbased study suggest that induced abortions have no overall effect on the risk of breast cancer, regardless of age.26
Other factors that may be associated with increased breast cancer risk for younger women include: a history of proliferative benign breast disease; nulliparity, low parity, or late age at first full-term pregnancy; and short duration of breastfeeding or never having lactated.24 Current or recent use of combined oral contraceptives is associated with a slightly increased risk of breast cancer, but there is no evidence of excess breast cancer risk 10 or more years after cessation of oral contraceptive use.25 A link between induced abortion and breast cancer risk has been hypothesised, but the results of a large, populationbased study suggest that induced abortions have no overall effect on the risk of breast cancer, regardless of age.26
breast cancer mortality
Epidemiological studies suggest that younger women with breast cancer have worse disease-free and overall survival outcomes.14-19 Evidence about whether independent predictors of disease-free and overall survival outcomes are similar across various age groups is inconclusive. However, positive nodes and tumour size appear to be important independent discriminators across all ages (see Table 1).
breast cancer characteristics
In 1999, 89 Australian women aged younger than 40 years and 347 women agedbetween 40 and 49 years died from breast cancer (see Table 1). Over the fouryear period between 1992 and 1996, the risk of death from breast cancer was 1 in 27,517 for women aged less than 30 years, 1 in 1,317 for women aged 30 to 39 years, and 1 in 366 for women aged 40 to 49 years.11 Breast cancer mortality for younger women remained relatively stable over the ten-year period between 1986 and 1996.11
Breast cancers in younger women have a different distribution of pathological features. While there are some inconsistent findings across studies, overall there appears to be an increased incidence of several features that have been shown to predict adverse outcomes. These include larger tumour size, more positive nodes, negative steroid hormone receptors and higher histological grade.20,21, Poorer outcomes for younger women could be partly due to differences in these prognostic factors.There is little published population-based research to clarify the impact of young age on disease outcome; however, two well conducted studies have concluded that young age is an adverse predictor of disease outcome in certain subgroups. A Danish study found that although age was an independent predictor of outcome, the negative effect of young age was almost exclusively seen in women classified as having low-risk disease who did not
receive adjuvant therapy.17 A report from the International Breast Cancer Study Group (IBCSG)15 provided data about 3,700 pre- or perimenopausal women with early stage breast cancer who received adjuvant chemotherapy in successive randomised trials between 1978 and 1993. Women aged younger than 35 had significantly shorter disease-free survival than older women and, among the younger women, positive oestrogen receptor status was associated with a particularly high risk of recurrence, possibly related to the absence of treatment with endocrine therapy.
Breast cancers in younger women have a different distribution of pathological features. While there are some inconsistent findings across studies, overall there appears to be an increased incidence of several features that have been shown to predict adverse outcomes. These include larger tumour size, more positive nodes, negative steroid hormone receptors and higher histological grade.20,21, Poorer outcomes for younger women could be partly due to differences in these prognostic factors.There is little published population-based research to clarify the impact of young age on disease outcome; however, two well conducted studies have concluded that young age is an adverse predictor of disease outcome in certain subgroups. A Danish study found that although age was an independent predictor of outcome, the negative effect of young age was almost exclusively seen in women classified as having low-risk disease who did not
receive adjuvant therapy.17 A report from the International Breast Cancer Study Group (IBCSG)15 provided data about 3,700 pre- or perimenopausal women with early stage breast cancer who received adjuvant chemotherapy in successive randomised trials between 1978 and 1993. Women aged younger than 35 had significantly shorter disease-free survival than older women and, among the younger women, positive oestrogen receptor status was associated with a particularly high risk of recurrence, possibly related to the absence of treatment with endocrine therapy.
breast cancer incidence in young woman
In 1999 there were 10,592 new cases of breast cancer diagnosed in women in Australia. Of these, 684 cases (approximately 6%) were in women aged younger than 40 years, while 1,967 cases (approximately 19%) were in women aged between 40 and 49 years (see Table 1).10
The risk of developing breast cancer increases with age. Over the four-year period between 1992 and 1996,Australian women aged less than 30 years had a 1 in 2,298 risk of developing breast cancer,women aged 30 to 39 years had a risk of 1 in 244, and those aged 40 to 49 had a 1 in 67 risk.11 Over the ten-year period between 1986 and 1996 there was a rise of 7% in the breast cancer incidence rate for women aged 15 to 39 years.11 Although breast cancer incidence is lower in younger women, the years of life lost in this age group is proportionately greater due to their longer life expectancy.
The risk of developing breast cancer increases with age. Over the four-year period between 1992 and 1996,Australian women aged less than 30 years had a 1 in 2,298 risk of developing breast cancer,women aged 30 to 39 years had a risk of 1 in 244, and those aged 40 to 49 had a 1 in 67 risk.11 Over the ten-year period between 1986 and 1996 there was a rise of 7% in the breast cancer incidence rate for women aged 15 to 39 years.11 Although breast cancer incidence is lower in younger women, the years of life lost in this age group is proportionately greater due to their longer life expectancy.
breast cancer in young woman
There is no accepted definition of ‘young’ as it applies in the context of breast cancer. For the purposes of these guidelines, younger women are defined as women aged 40 years or less at breast cancer diagnosis, unless otherwise indicated. However, it should be recognised that many issues that are relevant to the clinical management and support of these women may also be pertinent for women of other age groups, depending on their life stage.
There are varied age classifications used for ‘younger’ and ‘older’ in the literature. For example, in clinical trials participants are often classified according to menopausal status:‘younger’women are premenopausal and/or aged less than 50 years, and ‘older’women are post-menopausal and/or aged 50 years or older.1 Many pathological studies report specific results pertaining to women aged 35 years or less; these studies suggest that disease factors appear to be different for this age group compared with older women.2 A range of age classifications is also employed in the psychosocial literature. Studies variously define ‘younger’ as less than 60 years,3 less than 50 years,4-6 less than 45 years,7 or less than 40 years.8 Other researchers have avoided using chronological age, instead relying on defining indicators such as having young children, not having reached menopause, and being of child-bearing age.9
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