Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / @xirurgi_2025 / @xirurgi_2025 - 881 - файл
.pdf
98
Screening (GISMa). The consensus statement was that breast cancer prevention
programs for women of over 70years should be extended [5]. Subsequently, in 2007
the International Society of Geriatric Oncology (SIOG) created a task force with the
aim of developing multidisciplinary guidelines for the treatment of breast cancer in
elderly women. More recently in 2012, these recommendations were updated by
SIOG in association with the European Society of Breast Cancer Specialists
(EUSOMA) [1]. In their statements, the SIOG and EUSOMA task force reiterate
that elderly patients rarely undergo standardized therapies and have a higher rate of
treatment interruption [1].
At the same time, the Italian Association of Medical Oncology (AIOM) added a
chapter dealing with the specic treatment of breast cancer in older women, as part
of their national clinical practice guidelines for oncology [6].
M. Francucci et al.
7.2 Epidemiology
In Italy, breast cancer is the most frequent cancer in women (29% of all cases) [6]:
41% in the age group 0–49years, 35% in the age group 50–69years, and 21% in
cases of women over 70years of age [7–9]. In the USA, over 40% of women of 65+
years of age develop breast cancers; in 20% of them, diagnosis is made in women
of 75+ years of age [7]. Aging is one of the main risk factors for breast cancer:
patients of up to 49years of age show an incidence rate of 2.4% in the diagnosis of
new breast cancer, while those of over 70years of age show a higher incidence trend
of 4.7% [6]. Age is not an independent risk factor for the development of new breast
cancer but is a result of the increased period of exposure to carcinogenic factors. As
a result of the progressive increase in life expectancy, in the years to come, there
will be a consequent signicant increase in breast cancer rates in women >80years
of age.
In Italy in 2014, 16% of deaths caused by breast cancer were reported in women
70+ years of age [7]. Breast cancer is also the leading cause of death in women of
all age groups: 29% of deaths by cancer before age 50, 21% between 50 and
69years, and 16% after 70years [10]. The SEER (Surveillance, Epidemiology, and
End Results) study showed that in these women, mortality is not only related to
cancer but also related to general comorbidities. In women of over 70years of age,
the deaths were not related to malignancy. In effect 80% of deaths occurred in
patients without lymph node involvement (N) conversely and 60% in women with
lymph node involvement (N+) [11].
7.3 Biological andHistological Characteristics
Breast cancer in the elderly woman has a prognostic prole more favorable than
that of the younger woman; in fact, with aging the risk of local recurrence after
surgery decreases [12]. In geriatric patients, the anatomical and pathological features of breast cancer are not signicantly different from those of other age groups.
7 Breast Cancer Management intheOlder Woman
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
99
Unfortunately, invasive ductal carcinoma prevails, even if there is a greater frequency in some better prognosis histology. In effect, papillary carcinoma and mucinous carcinoma have a higher incidence after 75years of age (4–6%) compared to
women of childbearing age (1%) [13]. Neoplasms diagnosed in old age are associated with more favorable biological factors as well as a reduced aggressiveness.
These characteristics are represented by lower aneuploidy [14] as well as lower
expression of HER-2 (20.8%), Ki67 (33.7%), p53 (39.2%), EGF receptors (19.8%)
and a greater expression of estrogen receptors (70.5%) and progesterone (56.7%)
[15, 16].
In elderly women, breast cancer presents a greater degree of differentiation and
a lower cell proliferation index: characteristics, which condition a slower neoplastic
doubling time and a reduced tendency to develop both loco-regional recurrence and
systemic metastasis [14]. These features seem to be at odds with the higher incidence rates of advanced cancer diagnosed in the elderly. Because of this, there is an
erroneous oncologist opinion that these “more aggressive” tumors are associated
with a poor prognosis [17]. Conversely, locally advanced tumors are often due to
multiple factors including the failure to extend mammography screening to the over
70, along with a generally delayed diagnosis. This high risk of missed or delayed
diagnosis is due to the reduced inclination of older women to undergo a breast
assessment, even in the presence of clinical signs and symptoms. Another element
is the disparity of access to the health-care system (the absence of family stimulus
and poor compliance, scarce economic resources, travel difculties, as well as availability of somebody to accompany them).
7.4 Role ofMammographic Screening
Mammography screening, performed in the age group between 49 and 69years, has
dramatically reduced mortality due to breast cancer [18]; based on this data, the
possibility of extending mammographic screening up to 74 years has been suggested [19]. The role of mammographic screening in determining mortality reduction has been clearly shown in women of over 70+ years old who have a life
expectancy greater than 10years and who have a good performance status [14, 20,
21]. Moreover, mammography in geriatric-aged patients presents a sensitivity and
specicity similar or greater than in younger patients; consequently, there is a
greater predictive value and lower cost for each breast cancer diagnosed in these
elderly women.
In 2006, the Italian Group for Breast Cancer Screening (GISMa) organized a
national consensus conference on this topic. They recommended the extension of
mammographic screening up to 74years of age, where local health-care resources
permit. This screening prolongation is only appropriate for women who had
responded to previous screening steps and had a good life expectancy.
As regards the rst point, the cost-effective analysis showed that the prolongation
of screenings up to 79years of age would require between $ 8000 and 27,000, considerably lower than the resources necessary ($ 24,000–65,000) for prolongation to
100
Table 7.1 Life expectancy/age
Percentage
Age
50 20.5 21.5 36.5 415 45.5
60 16.5 17.5 26.5 31.5 35.5
65 12.5 12.5 21.5 26.5 30.5
70 9.5 11.5 17.5 22.5 26.5
75 3.5 8.5 12.5 17.5 21.5
10° 25° 50° 75° 90°
M. Francucci et al.
40–49 age group [22]. For these reasons, the age limit for mammographic screening
has been prolonged to 75years of age in many European countries and the USA [21].
Although the prolongation of the age range for screening has some critical aspects,
with the increase of age, there is a progressively reduced adhesion to screening programs, and the expected benets of such prevention programs manifest themselves
after 6–8years of their launch (Table7.1) [23]. Based on this evidence, some Italian
regions have prolonged mammographic screening up to 74years of age:
– The Region of Emilia-Romagna, in January 2010, prolonged screening to women
between 45 and 74years of age.
– The Region of Umbria, in April 2013, prolonged the screening program up to
74years.
– The Region of Tuscany, in September 2016, prolonged the screening program to
women aged 70–74years, who had participated in one of the two previous calls
before the age of 70.
– The Region of Basilicata, in December 2016, prolonged mammography screen-
ing to all women from 45 to 74years old.
– The Region of Lazio offered the opportunity of free mammogram for women
between 70 and 74years, during the “Pink October” festival.
– The ASL of Milan offered the screening program to women aged 50–74years
who are resident in the territory of the ASL Milan.
In cases where age prolongation for mammography screening is not possible,
GISMa recommended facilitating access to spontaneous screening or providing
specic diagnosis/treatment planning. Here, the family physician, who is familiar
with the general health of his/her patients, plays a fundamental role: regulating
access to spontaneous screening, implementing clinical breast evaluation during
follow-up control, as well as instructing regular self-inspection [19].
7.5 Organizational Models
The EUSOMA recommended targeting women with breast cancer in specialist
breast centers (Breast Units). Here, in the light of the heterogeneity of breast cancer,
a specic and effective therapy guaranteeing a higher percentage of survival and a
better quality of life to every woman is available [24]. In the Breast Unit, all
7 Breast Cancer Management intheOlder Woman
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
101
decisions arrived from collaboration between various medical specialists and strictly
upon evidence-based medicine (EBM). The patient’s point of view plays a critical
role here; it is essential for a successful treatment, as well as occupying a critical
role in the management of treatment. It has been shown that, in the elderly patient,
an accurate information and an active participation in the diagnostic and therapeutic
process allow for an increased success and an improved quality of life [12].
Moreover, the Breast Unit plays an important role in facilitating specic diagnosis/
treatment planning, as well as reducing surgery waiting time.
In old age, the increased risk of postoperative complications, as well as frequent
functional and cognitive decline, requires a greater level of attention in the perioperative period. This higher level of clinical attention can only be guaranteed in geriatric surgical centers. Here surgeons, anesthetists, and nurses will be aware of the
specicities and the management of the complexities of aging. This mix of Breast
Units and geriatric surgery centers together carries out outpatient diagnosis, admission to hospital, preparation for surgery, and perioperative care, as well as early
rehabilitation and follow-up. To this end, the Italian Society of Geriatric Surgery
together with the Italian Chapter of the American College of Surgeons (ACS) has
contextualized the guidelines of the ACS and AGS (Geriatric Healthcare
Professionals) to the Italian health system [25].
Multidisciplinary geriatric assessment, already started in the outpatient phase,
serves to clarify the course of treatment, the risks associated with surgery, and the
acquisition of consent to treatment by the patient and her family entourage, especially important in women with reduced decision-making capacities. Frequent home
polypharmacotherapy represents a critical point typical of old age, due to potential
interactions with anesthetic drugs. For this reason, recognition and reconciliation of
drug therapy are essential, as recommended by health-care organizations.
In the elderly, the most serious postoperative complication is delirium, caused by
prolonged hospital stay. It is responsible for functional decline, higher rate of institutionalization in residential age care centers, as well as higher mortality rates. The
delirium rate is reduced by short postoperative hospital stay in designated facilities
of day/week surgery, as well as postoperative setup monitoring in order to ensure
optimal and early treatment of delirium.
7.6 Role ofPreoperative Evaluation
In geriatric patients, it is crucial to undertake a global assessment of health status,
through a multidimensional approach aimed at identifying their comorbidities and
functional status, cognitive, psychological, and nutritional, to choose the best treatment strategy. The main comorbidities responsible for reduced survival rates are as
follows: diabetes, kidney and/or liver failure, stroke, previous diagnosis of cancer,
and cigarette smoking. It has been shown that in the age group between 65 and
74years, there are on average three comorbidities, but in the age group between 75
and 84years, there are on average four comorbidities, and in ≥85years there are
ve comorbidities [26].
102
Table 7.2 Categories of aging
Patients Characteristics
Fit Absence of functional dependence
Vulnerable Presence of one or more aspects on the IADL scale
Frail Presence of one or more of the following aspects
IADL instrumental activity of daily living; ADL activity of daily living
a
Severe episodes, possibly evidenced by neurologist or psychiatrist
b
At least three times a month, particularly in well-known environments, such as the home
c
Body mass index minor or equal to 20
d
Irreversible and nonassociated to cancer or radiotherapy/surgical treatment
e
Disabilities associated with pathological fractures
No signicant comorbidities
Stable comorbidities (e.g., stable angina, chronic renal insufciency, etc.)
Dependence on one or more of the ADL aspects
Three or more comorbidities or one uncompensated comorbidity
One or more geriatric syndromes (depression, dementia, delirium
personal care, inability to put on weight
osteoporosis
e
)
c
, urinary and/or fecal incontinenced,
M. Francucci et al.
a
, fallsb, poor
Geriatric assessment is especially important in frail patients, for whom it is necessary to implement measures aimed at maintaining functional status. In addition to
identifying any comorbidities present, multidimensional geriatric evaluation allows
us to highlight any psychophysical limitations, the presence or absence of social
support, as well allowing for the stabilization of risk factors, thus improving compliance, tolerability to treatment, and quality of life [1, 27]. Global evaluation, using
validated scales, allows for the creation of a socio-targeted health intervention plan
for each individual patient.
The most frequently used tool for the evaluation of geriatric patient as global
assessment is the Comprehensive Geriatric Assessment (CGA), which has a systematic approach aimed at evaluation of multiple aspects: autonomy level, presence or
absence of comorbidities, nutritional status, pharmacotherapy, cognitive function,
and emotional state [28]. The use of the CGA allows for the categorization of elderly
patients into three proles: t, vulnerable, and frail (Table7.2) [29]. In common
clinical practice, this assessment is not yet included as a routine test since in the
literature concerned there is still no sufcient evidence to consider CGA as a mandatory practice in the management of older women with breast cancer [30]. In geriatric surgical centers involved with the routine use of the CGA, it allows for
identication of the most appropriate plan for the specic conditions of individual
elderly patients (“made to measure” surgery) [31].
7.7 Therapeutic Strategy
In the past, breast cancer surgery required a more aggressive approach (mastectomy
sec. Halsted) to obtain a maximum loco-regional disease control (Fig.7.1). On the
other hand, in the 1980s, Fisher suggested that breast cancer is a systemic disease,
requiring less extensive surgery than that associated with improved systemic control
by means of chemoradiotherapy [32].
(Quadrantectomy,
Axillary Dissection, and
Radiation Therapy)
Sentinel-node biopsy
Geriatric Oncology (SIOG) an
European Society of Breas
Cancer Specialists (EUSOMA)
Geriatric Oncology (SIOG
7 Breast Cancer Management intheOlder Woman
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
U. Veronesi
(1925-2016).
WS Halsted
(1852-1922)
H. Patey
(1889-1977)
103
d
)
t
Halsted
mastectomy
1894 1948 1969 1997 2006 2007 2012
Patey
mastectomy
QUART
International Society of
Recommendations of the
International Society of
Recommendations of the
Fig. 7.1 Surgical history of treatment of breast cancer in older women
Over the years, the management of breast cancer in older women used to be very
heterogeneous: ranging from radical mastectomy to hormone therapy alone. During
this period, various surgical techniques have been proposed: ranging from mastectomy with axillary dissection to simple mastectomy or wide lumpectomy. These
changes of treatment options were supported by an alleged minor surgical risk than
radical mastectomy, even if the failure to perform a complete axillary lymphadenectomy did not allow an adequate nodal oncological staging [33]. Hormone therapy,
especially in women with closely related concomitant conditions of reduced life
expectation, was proposed as a wise alternative to surgery.
The absence of a standardized procedure was the result of the lack of scientic
evidence from clinical studies. Subsequently the execution of well-organized scientic studies has allowed the development of guidelines based on evidence-based
medicine. In fact, in 2007 the guidelines produced by the multidisciplinary task force
of the SIOG, subsequently updated in 2012 by SIOG and EUSOMA, suggest that
women from 70years onwards with the absence of signicant comorbidities should
receive the same surgical treatment as offered to younger patients [6]. Currently, the
standard of care is represented by BCS followed by radiation therapy (statement by
SIOG and EUSOMA 2012). Mastectomy is advised only in the following selected
cases: large or multifocal tumors, which cannot be treated by BCS alone, patients
who cannot undergo postoperative radiotherapy, as well as for patients who prefer
such intervention rather than BCS (statement by SIOG and EUSOMA 2012) [
6].
7.7.1 Surgical Management
Even in older women, the recommended surgical choice is BCS.As reported by
Umberto Veronesi, surgical senology has progressed “from the maximum tolerable
to the minimum effective treatment” [34].
104
M. Francucci et al.
BCS is followed up by radiotherapy on what remains of the breast, in order to
reduce the incidence of loco-regional recurrence. This therapeutic approach is recommended in DCIS (ductal carcinoma in situ), except in the presence of absolute
contraindications (previous irradiation of the breast region, multifocal DCIS, microcalcications of suspicious malignancy nature, as well as mastitis carcinomatosa) or
related contraindications (difculty in obtaining good aesthetic results, poor tumor/
breast volume ratio, patient refusal to undertake the quadrantectomy associated with
radiotherapy) (AIOM 2016 guidelines) [7]. In such cases, mastectomy is carried out
with subsequent breast reconstruction wherever this option is possible [35].
Currently, the opinion that old age does not bring about higher surgical risk is
shared by all. Thanks to advances in anesthetic techniques with local anesthesia, it
is possible to carry out a wide range of breast surgical techniques, including simple
mastectomy. This represents an undoubted benet for women with a high rate of
comorbidities. In 2012, Kaur published a retrospective observational study of 1028
patients aged up to 70years versus 4207 younger patients; the 30 and 90 postoperative day mortalities were similar in the two groups, respectively, 0.2% in the elderly
group versus 0 among younger patients and 0.9% in the elderly group versus 0.05%
among younger patients [36].
7.7.2 Reconstructive andOncoplastic Surgery
NICE guidelines highlight the lack of studies in oncoplastic and reconstructive surgery, which reects an underutilization of these techniques in geriatric patients. In
the literature concerned, few studies report the long-term follow-up of breast reconstruction with the use of prosthesis or with autologous techniques [37]. Since the
percentage of cases in which breast reconstruction is offered decreases with age,
similarly, it reduces the rate of acceptance by the patients [35]. In fact, breast reconstructive surgery performed in the elderly is not burdened by increased mortality. In
women aged less than 65years, Lipa etal. reported a 10-year survival rate of 91%
for those who had undergone reconstruction with implants and 88% for those who
had undergone the TRAM procedure [38].
These benets are also reported in the National Health Service (NHS) guidelines.
Women who accept reconstruction are generally satised with their treatment and afrm
an improved quality of life [35]. James, despite the small number of patients enrolled,
feels autologous techniques are safer, in spite of an increased invasiveness and a longer
operative time [35]. On the other hand, Selber suggests reconstruction with prosthetic
implants to shorten operative time, despite the risk of a higher frequency of postoperative complications [39]. It is recommended that autologous reconstruction should be
considered an option only in women with an acceptable risk prole.
NICE guidelines reafrm that, at the time of the strategy proposal, a therapeutic
strategy for older women should not be discriminatory on the basis of chronological
age alone. Each woman should receive the most appropriate treatment for her medical condition and comorbidities, over and above the preconception that a woman in
geriatric age has a different perception of her aging body (Table7.3).
7 Breast Cancer Management intheOlder Woman
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Table 7.3 Offer of breast reconstruction. Acceptance percentage by patients
Age (years)
<40 60 43
50 60 35
60 53 20
70 45 8
80 18 2
Offered reconstruction (%)
Accepted reconstruction (%)
105
In this regard, the UK All-Parliamentary Group on Breast Cancer published the
recommendations from its inquiry into breast cancer in older woman and recommends nondiscrimination on the basis of age. To ensure greater compliance of the
elderly woman to the therapeutic process, it is essential that at the time of diagnosis
and during the brieng, the possibility of breast reconstruction should also be proposed. James, according to his experience and a systematic review of the literature,
believes that breast plastic remodeling (oncoplastic) could be considered a viable
alternative to mastectomy. In geriatric patients, the oncoplastic option is considered
to be a safe procedure and does not determine a greater surgical risk. The incidence
of postoperative complications, length of hospital stay, and recovery time do not
differ between the different age groups.
The oncoplastic procedure also presents several advantages:
– Wider local breast excision, since it allows a greater probability of obtaining
margins free of cancer cells, with a consequent reduction in the number of reop-
erations for loco-regional recurrence
– Better cosmetic results since the breast of older women has an increased propor-
tion of fat tissue [35]
In conclusion, oncoplastic and reconstructive breast surgical techniques are considered safe even for elderly women.
7.7.3 Axillary Lymphadenectomy
In the past, axillary lymphadenectomy, performed with double diagnostic and
therapeutic targets, represented the gold standard to obtain a more complete staging and oncological radicality, ensuring an improved prognosis. Subsequent studies showed that this surgical approach was excessive in both younger and older
groups. The Fisher study (NSABP B-04), carried out on patients of all ages, without clinical lymph node involvement, did not show statistically signicant differences between radical mastectomy versus simple mastectomy with or without
radiotherapy [32]. Similar results, in a retrospective study of 671 patients aged
≥70 years with operable breast cancer and clinically negative axillary lymph
nodes, were reported by Martelli; he detected no signicant differences in mortality during a follow-up of 15years between the two groups: axillary dissection
versus tamoxifen alone [40].
106
M. Francucci et al.
NICE guidelines recommended that patients with invasive breast cancer, without
lymph node involvement on ultrasound or negative lymph node biopsy, should
undergo axillary sentinel node biopsy, correlated to lower morbidity than the complete axillary dissection as well as avoiding upper arm lymphedema [41]. Thus, the
introduction in common clinical practice of sentinel node biopsy has completely
revolutionized axillary management.
The SIOG/EUSOMA guidelines recommended axillary dissection alone for
elderly patients with clinically positive or highly suspected nodes; in such patients,
sentinel node biopsy should avoid an unnecessary axillary dissection [1, 6].
7.7.4 Radiotherapy after Breast-Conserving Surgery
The role of radiotherapy after breast-conserving surgery in elderly patients is highly
controversial.
The CALGB 9343 study was conducted on women aged ≥70 years with
ER-positive tumors CT1 CN0 (clinical stage I), undergoing BCS and subsequently
randomized for treatment with radiotherapy (WBRT)+tamoxifen versus tamoxifen
alone. This RCT showed only an 8% reduction in the loco-regional recurrence rate
at 10-year follow-up in-group undergoing radiotherapy, without reduction of the
risk of distant metastasis and/or cancer-related mortality [42].
These results seem at odds with other studies, which showed better overall survival rates in radiotherapy groups [1]. Also the Veronesi RCT, which compared
quadrantectomy alone with quadrantectomy + radiotherapy, shows lower local
recurrence rates in over 55-year-old women than in younger patients not undergoing
radiation therapy [43]. Furthermore, the rst 248 study has reported that in elderly
patients undergoing hormone therapy after BCS treatment for low-grade tumors and
hormone receptor-positive and receptor-negative axillary lymph nodes, there is a
low recurrence rate [44].
For these reasons, the omission of postoperative radiotherapy may be considered
a viable treatment option in elderly women, undergoing BCS (clinical nodes negative, ER positive), who are receiving adjuvant hormonal therapy. In this regard, the
British Association (BASO) suggested that tamoxifen probably has the same effectiveness as radiation therapy in reducing local recurrence among low-risk women
undergoing BCS [45].
7.7.5 Hormonotherapy
In the older woman, hormone therapy alone, due to frequent association with more
closely related comorbidities, represents a viable alternative to surgery.
The data resulting from the GRETA study [46] and by the study of Gazet [47]
have shown that surgery followed by tamoxifen presents a higher disease-free survival (DFS) rate even though it does not change the overall survival rate. A systematic review and meta-analysis (Cochrane review) conrmed that surgical treatment
7 Breast Cancer Management intheOlder Woman
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Geriatric assesment in older
women with breast cancer
Non Frail Frail
107
Fit
«The same
surgery as
younger
patients»
(full treatment)
Fig. 7.2 Algorithm of surgical treatment of breast cancer in older women
Vulnerable
Rehabilitation
Persistent
Vulnerability
Palliative
treatment
Tailored
surgery
with or without tamoxifen is superior to tamoxifen alone in terms of overall survival
(OS), progression-free survival (PFS), and local recurrence [48].
Since the DFS and the quality of life are the main end points of breast cancer
treatment of elderly patients, an endocrine treatment with tamoxifen or aromatase
inhibitors can still be considered for older women with ER-positive tumors and poor
general condition or those who refuse surgery.
Conclusion
Current opinion shared by the international scientic community (SIOG and
EUSOMA) is that the surgical approach to breast cancer in elderly woman should
always have the same radical oncological aim, regardless of the chronological
age of the patient concerned.
The prevalence of any comorbidities, associated with the aging process, can
have a negative impact on major surgical postoperative outcomes, such as 30-day
postoperative morbidity and mortality, as well as the length of hospital stay.
For this reason, in order to identify the most appropriate management, an
accurate multidimensional evaluation of the health status and life expectancy of
the patient is essential from a clinical point of view, in order to avoid undertreatment of breast cancer, which could lead to disease recurrence and death [49].
As a result, treatment should be individualized for each elderly woman in
order to perform a “tailored surgery” [31]. BCS is the gold standard of care.
Hormone therapy alone should be reserved only for patients with severe comorbidities, the “frail” for surgery, or for those who refuse surgery (Fig.7.2).
Acknowledgments We thank Nicholas J.Collerton for his collaboration and translation.
Соседние файлы в папке @xirurgi_2025