general management 02

Management of Lobular Carcinoma in Situ

LCIS appears to arise from the terminal duct-lobular complex and is
considered to be a marker of increased risk for invasive carcinoma.
[ref: 273] It is estimated to comprise approximately one third of all
in situ lesions of the breast. Women with a diagnosis of LCIS have a
10% to 37% risk of later developing invasive breast cancer
(Table 50-17).

The diagnosis is usually made in premenopausal women between 35 to 55
years of age (10 to 15 years younger than patients with invasive
breast cancer). [ref: 308] LCIS is invariably an incidental histologic
finding in breast biopsies, because the lesions are not palpable in
breast tissue and are generally invisible to the naked eye. [ref: 747]

LCIS has a high incidence of multicentricity ranging from 48% to 80%
[ref: 621] and bilaterality ranging from 18% to 67%. [ref:
100,202,742] The incidence of multifocal carcinoma of the breast was
reported to be about 20% in DCIS and 7% in 496 patients with invasive
ductal carcinoma, in contrast to 45% to 54% in 92 patients with
invasive lobular carcinoma. [ref: 302] In more than half of the
patients, the foci were in the same quadrant as the primary tumor, and
they were in the adjacent quadrant in 30%. In Farrow's study [ref:
202] of 270 women with LCIS, 33 (12%) had simultaneous bilateral LCIS,
16 (6%) developed subsequent contralateral LCIS (for a total of 18%
with bilateral disease), and 70 (26%) had previous, simultaneous, or
subsequent cancer.

Simkovich and associates [ref: 693] reported that 17% of contralateral
biopsies in lobular breast cancer (in situ or invasive ductal
carcinoma) were indicative for further therapy.

For many years, management of LCIS generally consisted of biopsy of
the involved and the contralateral breast. [ref: 706] In 1974, Wheeler
and associates [ref: 841] argued against mastectomy and proposed
careful lifelong follow-up for patients with LCIS, an approach that is
favored by most surgeons at the present time. [ref: 299,543,829]

The risk of a second breast cancer developing averages about 0.7% per
year, with a cumulative incidence of bilateral breast cancer of 4% to
26%. [ref: 433] Two thirds of the second breast cancers are
metachronous.

An important issue is whether patients with LCIS warrant therapeutic
intervention at initial diagnosis, because some may subsequently
develop invasive carcinoma, the risk in either breast being fairly
equal. In the series from Haagensen and associates [ref: 308] of 211
untreated cases of LCIS with a mean follow-up of 14 years, the overall
probability of developing invasive cancer in the ipsilateral breast
was 10%, and in the contralateral breast, 9%. In patients monitored
for 16 to 25 years, the risk of invasive cancer increased to 22% in
the ipsilateral breast, compared with 15% in the contralateral breast.
These authors recommended close monitoring for patients with LCIS
because of the equal risk of cancer in both breasts and the long
interval to the development of invasive cancer.

Confirming these findings, Rosen and colleagues [ref: 619] reported on
84 patients with LCIS with an average follow-up of 24 years after
biopsy only. The incidence of subsequent invasive carcinoma was 14% in
the ipsilateral breast, 14% in the contralateral breast, and 8% for
bilateral cancers. Overall, 36% of patients later developed invasive
cancer. In contrast, in a study of 149 patients with carcinoma of the
breast in whom a diagnosis of in situ carcinoma was confirmed, among
those treated by local excision, ipsilateral cancers were subsequently
seen in 12% of patients with DCIS and 13% of patients with LCIS. [ref:
761] Contralateral metachronous invasive cancers were seen in 6% of
the DCIS patients and 3% of the LCIS patients. No lymph node
involvement was seen in any of these patients, either with
prophylactic dissection or in follow-up. Seventeen of 109 patients
(15%) with intraductal lesions treated with local excision had local
recurrence; in contrast, in 7 of 40 patients with LCIS treated by
local excision, 2 had recurrences and 1 additional patient developed
invasive tubular carcinoma in the ipsilateral breast. The authors
concluded that both in situ lesions had similar clinical courses, that
treatment (ranging from local excision to modified or radical
mastectomy) did not appear to affect prognosis, and that lymph node
dissection was not necessary.

In a review of 3327 breast carcinomas, 47 were diagnosed as LCIS.
[ref: 461] Lesions were an incidental mammographic finding. Among 33
patients observed after local excision of the tumor, 1 (3%) developed
invasive carcinoma in the contralateral breast.

Lee and colleagues, [ref: 433] in a review of 419 women, found
bilateral lobular breast cancer in 36 patients (8.6%), with a
cumulative risk of 10% after 10 years. Prophylactic contralateral
surgical procedures were performed in 105 women and led to detection
of 70 in situ and 4 invasive cancers. Patients undergoing
contralateral prophylactic mastectomy had a better prognosis than
those with unilateral tumors not treated prophylactically. However,
there was no survival benefit, and the authors believe that
contralateral prophylactic mastectomy should not be recommended.

Page and associates [ref: 554] noted that the incidence of invasive
carcinoma after LCIS at 15 years was 17% and the recurrence rate was
8%. LCIS is considered a marker for malignancy rather than a
premalignant lesion per se; because this applies to both breasts, the
appearance of an invasive lesion can be a slow process (80% to 85%
disease-free survival at 15 years). Since many recurrences can be
successfully treated, observation is an acceptable form of management
in most patients. [ref: 140] Partial mastectomy has been used in the
treatment of these patients. [ref: 75,299,606] Recurrences (either
LCIS or infiltrating carcinoma) were observed in 1.5% to 21% of
patients, and long-term mortality after mastectomy for recurrence
ranged from 0% to 8.1%.

Temple and colleagues [ref: 761] reported on 109 patients with DCIS,
38 patients with LCIS, and 3 with both, who were treated with surgery
ranging from local excision to radical mastectomy. Among the patients
treated with local excision, ipsilateral breast recurrences were seen
in 12% of those with DCIS and 13% of those with LCIS. No lymph node
involvement was seen in any patient, either in node dissection or on
follow-up. Contralateral metachronous invasive breast cancers were
seen in 6% of those with DCIS and 3% of those with LCIS.

Singletary [ref: 696] described her experience in 45 women who had
LCIS alone and 30 women who had LCIS associated with an ipsilateral
stage I or II breast carcinoma but no abnormality in the opposite
breast. There was a 1% incidence of synchronous and 5% incidence of
metachronous nonlobular carcinoma in situ breast cancer in the
contralateral breast. Another breast cancer developed in a different
quadrant in 3 (16%) of 19 women with ipsilateral residual or intact
breast tissue. The author endorsed the recommendation of lifelong
careful observation of patients with LCIS. Surveillance should consist
of monthly self-examination, physical examination of the breast every
3 or 4 months, and annual mammography.

A metaanalysis of 13 reports concerning surgical management of LCIS
and 12 reports on DCIS after local excision showed recurrence rates of
17% with DCIS and 8.4% with LCIS. [ref: 75] The overall mortality
rates after mastectomy for patients with postexcision recurrence were
2.3% for DCIS and 2.8% for LCIS, not statistically different from the
rates for patients initially treated with mastectomy (1.7% for DCIS
and 0.9% for LCIS). Therefore, treatment options for LCIS are complete
local excision of the lesion and close follow-up, ipsilateral total
mastectomy with or without contralateral "mirror" biopsies, bilateral
mastectomies, or hormonal manipulation in investigational protocols.
[ref: 745] However, because 20% to 30% of women with LCIS later
develop invasive carcinoma in either breast, often after a great
number of years, excisional biopsy with close follow-up appears to be
the most reasonable approach. Nevertheless, Singletary [ref: 696] and
Morrow and associates [ref: 517] note that prophylactic bilateral
total mastectomies with breast reconstruction may be indicated in
highly anxious patients. Bilateral mastectomy for LCIS should be
considered only in women who have a strong family history of breast
cancer consistent with a hereditary pattern. [ref: 541]

Currently, there is no information regarding the use of breast
irradiation in LCIS.

Invasive Breast Tumors

Management of invasive breast cancer varies considerably among
institutions and physicians. However, treatment should be based on the
clinical extent and pathologic characteristics of the tumor, in
addition to the age of the patient (menopausal status), some biologic
prognostic factors, and the preference and psychological profile of
the individual patient. Patients with lesions smaller than 5 cm in
diameter and some specific characteristics to be discussed later
should be offered available options, with each modality thoroughly
discussed. In some states, legislation has been enacted requiring
treating physicians to comply with this practice.

For many years radical or modified radical mastectomy was considered
the standard therapy for operable patients. [ref: 216,306,785] Total
mastectomy combined with irradiation to the chest wall and regional
lymphatics has been used with comparable results. [ref: 229,380,491]

Alternatively, for more than 40 years, stage I and II tumors (T1, T2,
N0 or N1) have increasingly often been treated with local excision of
the tumor and breast irradiation. In recent years, several reports
have shown encouraging results with neoadjuvant chemotherapy, which
allows breast-conserving surgery and irradiation to be used in a large
proportion of these patients, because they exhibit substantial tumor
regression. [ref: 67,91,250,371] In response to a questionnaire mailed
to 2405 oncologists from all three disciplines and 60 oncology nurses
in the United States, Tannock and Belanger [ref: 752] noted that more
than 60% thought that modified radical mastectomy and conservation
surgery plus irradiation were equal options for patients with stage T1
and T2 carcinoma of the breast; 31% of the surgical oncologists
favored the former and 35% of the radiation oncologists favored the
latter approach. Medical oncologists were equally divided between the
two procedures (14% and 18%, respectively).

A modified radical mastectomy should be recommended, even for small
tumors, in patients with any of the following characteristics: (1)
patient preference -- cosmesis is not important, or desire to avoid 5
to 7 weeks of irradiation; (2) larger tumors in small breasts in which
a lumpectomy would remove so much tissue that the cosmetic outcome
would be severely compromised; (3) tumors with high risk for local
recurrence (e.g., EIC when negative margins are not attained); (4)
diffuse microcalcifications; (5) presence of skin or connective tissue
diseases that could be complicated by irradiation; and (6) patient
unreliable for follow-up.

Occasionally, after radical or modified radical mastectomy,
postoperative irradiation of the chest wall and peripheral lymphatics
is indicated in selected patients having high-risk characteristics,
regardless of the initial clinical stage or the administration of
adjuvant chemotherapy. [ref: 257,471] Although a few have claimed that
postoperative irradiation is harmful, [ref: 733] several analyses have
demonstrated that postoperative radiation therapy has no deleterious
effect and may even have a modest impact on overall survival. A study
in which adequate doses and fields of irradiation were used
demonstrated higher disease-free survival in patients treated with
irradiation before or after radical mastectomy compared those
undergoing mastectomy alone. [ref: 740] Postoperative irradiation is
discussed in detail in Chapter 51.

Premenopausal and postmenopausal patients who have poor prognosis are
treated with adjuvant chemotherapy. Bonadonna and associates [ref: 66]
described a beneficial effect in postmenopausal women who received at
least 85% of the prescribed doses of adjuvant chemotherapy. Levitt
[ref: 440] noted problems with interpretation of data in some major
clinical studies of adjuvant chemotherapy. Essentially, he concluded
that only premenopausal patients with fewer than three positive nodes
showed a benefit from this treatment.

Hormonal therapy has been extremely useful in many patients,
particularly those with positive ER or PR assay results. [ref: 453]
Procedures have included oophorectomy and adrenalectomy. Estrogens
have been used in premenopausal and postmenopausal patients as well.
Among women who are 4 years or more past menopause, estrogen
administration was successful in approximately 35% of patients.
Adrenal hormones, corticosteroids, progestins, and antiestrogens such
as tamoxifen are beneficial. [ref: 180,453,632]

Breast Conservation Therapy in Microinvasive Carcinoma

Microinvasive ductal carcinoma is defined as predominantly intraductal
carcinoma with microscopic or early invasion. Solin and co-workers
[ref: 717] analyzed 39 women with microinvasive ductal carcinoma of
the breast who were treated with breast-conserving surgery and
irradiation. Axillary lymph node staging showed 37 patients with
pathologically negative nodes and only 2 with positive nodes (each
with one positive lymph node). With median follow-up of 55 months, the
5-year actuarial overall and cause-specific survival rates were 97%.
Nine patients developed a recurrence in the breast; of 8 patients with
local-only first failure, 7 were salvaged with further treatment and
remained free of disease at last follow-up; 1 patient died of
subsequent distant metastasis. Median follow-up after salvage
treatment was 29 months (range, 0 to 54 months).

Bilateral Carcinoma of the Breast

Among factors reported to be associated with increased risk of
bilateral breast carcinoma are younger age, [ref: 63,104,351,445]
family history of breast cancer, [ref: 63,103,351,528,673] lobular
carcinoma, [ref: 351,359,445] multicentric disease, [ref: 528]
histologic differentiation of the primary tumor, parity status, [ref:
501] and positive PR assay. [ref: 359]

Patients with bilateral carcinoma have been treated with total or
modified radical mastectomy. [ref: 395] Breast irradiation combined
with tumor excision is an acceptable alternative therapy for
appropriately selected women with bilateral carcinoma of the breast.
Solin and associates [ref: 714] reported on 30 women receiving
radiation therapy after breast conservation surgery (11 with
concurrent and 19 with bilateral carcinoma). A dose of 45 to 50 Gy was
delivered to both breasts with tangential fields, in addition to a
boost of 10 to 15 Gy with either iridium implant or electrons. The
tangential fields were matched in the midline in 17 patients and
overlapped by up to 3 cm in 10 patients. Adjuvant chemotherapy was
given to 10 patients. The 5-year disease-free survival rate after
treatment of the first breast cancer was 79%, and the overall survival
rate was 72%. In the 60 treated breasts, the 5-year actuarial local
failure rate was 6%. In 25 treated breasts with a minimum of 2 years
of follow-up, 68% had excellent and 24% had good cosmetic results. The
incidence of arm edema was 6%, similar to that reported in patients
with unilateral disease.

In a review of 26 patients with stage I or II synchronous bilateral
breast cancer treated with breast-conserving therapy, the 5-year
actuarial cause-specific survival rate was 92%, and the disease-free
survival rate was 68%. [ref: 295] The incidence of local recurrence as
first failure site was 15% in the right breast and 4% in the left
breast. Distant metastases were the first site of failure in 12%.

Ninety-five patients with bilateral carcinoma of the breast treated
with mastectomy (60 patients), conservation of the breast (17
patients), or both (18 patients) were studied by Gustafsson and
associates. [ref: 303] Cumulative 5-year local tumor control rates
were 94% for the 138 mastectomy patients and 90% for the 52 patients
treated with breast conservation therapy. Distant metastases appeared
in one third of the patients; 50% occurred more than 60 months after
treatment. The 5-year distant disease-free survival rate from
treatment for the second carcinoma was 74%. Twenty-eight percent of
the first carcinomas were stage I, compared with 43% of second
carcinomas (P < 0.05); this result probably reflects the close
follow-up after initial treatment. The interval between the diagnosis
of first and second carcinomas had a profound effect on outcome; the
5-year distant recurrence-free survival rate when second carcinomas
were diagnosed within 5 years was 58%, compared with 95% for patients
diagnosed more than 5 years after the first carcinoma.

De la Rouchefordiere and co-workers [ref: 151] reported on 149
patients with simultaneous bilateral breast cancer (diagnosed within 6
months); of 298 tumors, 40% were T0 or T1, 45% were T2, and 15% were
T3 or T4. The majority (83%) were clinically node-negative. Treatments
were bilateral mastectomy in 43%, irradiation in 16%, and both in 41%
of the patients. Fifty-one patients had bilateral breast-conserving
therapy, and 24 were treated exclusively with irradiation. The 5-year
disease-free survival rates were 70% to 86%, similar to those observed
at the same institution in patients with unilateral tumors. Cosmesis
was assessed in 48 patients and was acceptable in 37 (77%). Special
attention should be paid to any possible overlap of the
supraclavicular and internal mammary fields over the spinal cord; one
patient developed spinal cord myelopathy at T6.

Paget's Disease of the Breast

This rare form of breast cancer comprises 1% to 4% of all breast
tumors. [ref: 23,251] Paget's disease of the breast is a carcinoma
that initially grows within the milk sinuses of the nipple, extending
into the ducts beneath the nipple in an apparently intraductal but not
necessarily in situ manner. [ref: 665] This disease may be
multicentric within the breast and may be associated with axillary
node metastases, although this is rare. Mammograms may demonstrate the
retroareolar spread of Paget's disease. Occasionally, calcifications
in a branching distribution may outline the intraductal spread. [ref:
667] Forty percent of patients have no evidence of a breast mass on
clinical or radiographic examination.

Many of these patients have been treated with mastectomy with
favorable results. [ref: 465,522] The role of limited surgery in
management of these patients has not been established; Lagios and
associates [ref: 424] noted one recurrence among five selected
patients treated with limited surgery only, and Paone and Baker [ref:
555] observed no recurrences in five patients treated with nipple
excision and wedge resection of the underlying breast.

Some patients have been treated with irradiation alone, without even
excision of the nipple-areola complex. This choice is feasible only if
the biopsy of the nipple indicates a relatively confined tumor. [ref:
667]

A few reports have been published on conservation surgery and
irradiation. Rissanen and Holsti [ref: 609] described results in 12
patients with Paget's disease of the breast without palpable mass
(minimum follow-up, 5 years); 9 patients had conservative treatment
with limited surgery, and 8 had radiation therapy. Radiation therapy
was delivered with 200-kV x-rays, and doses were lower than actual
standards. Tumor recurred in 3 patients, and 1 died of breast cancer.
Fourquet and colleagues [ref: 251] reported on 20 patients treated
conservatively with radiation therapy alone (17 patients) or limited
surgery and irradiation (3 patients). Most patients received 50 to 55
Gy to the breast and axillary lymph nodes and 40 to 45 Gy to the
external mammary and supraclavicular lymph nodes. The 7-year actuarial
disease-free survival rate was 81%, and the overall survival rate was
93%. Three patients had recurrence in the treated breast (nipple or
areola). One patient was treated with modified radical mastectomy and
the other two with simple mastectomy; all three patients were alive
with disease at 28, 77, and 98 months after salvage surgery. No
axillary failures were observed. Cosmetic results were satisfactory in
approximately 70% of patients. Although Fourquet and associates
irradiated the axilla, at the present time this is not recommended
because of the low incidence of axillary lymph nodes. [ref: 522]

Pierce and colleagues [ref: 574] reviewed 30 patients with Paget's
disease treated at several institutions with breast conservation
therapy (50 Gy) with a boost (14 Gy). None of the patients who
underwent axillary dissection had positive lymph nodes. With a median
follow-up of 62 months, three women developed a recurrence in the
treated breast, and two additional patients also failed in the breast
as a component of first failure. The 8-year local-only failure rate
was 16%; as a component of any failure, it was 23%. Four of five
patients were salvaged by mastectomy. The 8-year disease-free survival
rate was 95%.

Results of breast-conserving treatment for Paget's disease are shown
in Table 50-18.

Cystosarcoma Phyllodes

These rare fibroepithelial tumors account for fewer than 0.5% of
breast neoplasms in women. [ref: 605] Diagnostic workup is similar to
that used for breast masses.

Liberman and associates [ref: 446] reported mammographic findings in
46 women with 51 phyllodes tumors (32 benign and 19 malignant), 30 of
whom were also evaluated with preoperative sonography. On mammogram,
nonspiculated soft tissue masses were seen in 49 cases (96%); masses
were solitary in 48 and multiple in 1 case of recurrent benign
phyllodes tumor. Tumors 3 cm or larger had a greater relative risk
(3.87) of being malignant; six tumors larger than 8 cm were malignant.
Only 4 of 49 lesions (8%) contained calcifications visible on the
mammogram; 3 of them were benign, and 1 was malignant. Sonography
revealed cystic areas in 4 (44%) of 9 malignant tumors and 3 (14%) of
21 benign lesions (P = 0.15). In five tumors, doubling time was
calculated, and the median doubling time was 116 days (36 days for
malignant tumors, 105 to 638 for benign tumors).

Treatment for cystosarcoma phyllodes is either mastectomy or generous
wide local excision, depending on the degree of malignancy or size of
the lesion. Histologic grade appears to be the most important factor;
only about 10% of benign tumors recur. Size of the tumor has not been
shown to be a significant prognostic factor, but it may influence
surgical margins. However, the presence of underlying or clearly
malignant changes is associated with a higher recurrence rate and
distant metastases. [ref: 824]

Although few data support the use of radiation therapy in patients
with malignant cystosarcoma phyllodes, [ref: 824] from experience with
other types of histologic tumors in the breast it appears that
adjuvant radiation therapy may decrease the incidence of chest wall
recurrences, yet it may not have a significant impact on survival.
Patients with malignant cystosarcomas and positive or close surgical
margins and those who have local recurrence should be offered
radiation therapy to the breast or chest wall (50 Gy) to be followed
by a boost (10 to 15 Gy), depending on the presence of residual
microscopic or gross disease. Because of the low incidence of axillary
lymph node metastases, we do not advocate irradiation of the regional
lymphatics.

Cohn-Cedermark and associates [ref: 122] studied 77 patients with
primary cystosarcoma phyllodes of the breast; median age was 50 years.
Local recurrence was more common among patients treated with local
excision alone (13 of 24, 54%) than among patients treated with
mastectomy (2 of 53, 4%) (P < 0.001). However, there was no
significant difference between these two groups in terms of distant
metastasis-free survival (13% versus 25%, respectively). Sixteen
patients (21%) had distant metastases and subsequently died of
cystosarcoma phyllodes. With median follow-up of 8 years, 43 patients
(56%) were alive without disease, 6 (21%) were dead with disease, and
18 (23%) were dead with no evidence of disease. In a Cox multivariate
analysis, the only independent prognostic factors were tumor necrosis
(P < 0.05) and presence of stromal elements other than fibromyxoid
tissue (P < 0.01).

In a review of 170 cases, 92 (54%) were found to be benign, 59 (34.7%)
malignant, and 19 (11.2%) borderline. [ref: 605] Benign and borderline
tumors were usually treated with wide local excision, whereas the
malignant tumors were treated with simple (44%), modified (15%), or
radical mastectomy (34%). Mastectomy was recommended for recurrences
of borderline tumors and initially for malignant tumors. Lymph node
dissection was performed in 49% of the 59 patients with malignant
tumors; only 1 had node metastases. Postmastectomy irradiation to the
chest wall (50 Gy in 25 fractions) was administered in 4 patients with
infiltration of the pectoralis major muscle. Local recurrence was
found in 4 (4.3%) of 92 patients with benign tumors, 3 (15.8%) of 19
with borderline lesions, and 7 (11.9%) of 59 patients with malignant
tumors. With a mean follow-up of 8 years, the 5-year disease-free
survival rates in patients with malignant tumors were 65.5% (36 of 55)
after mastectomy and 75% (3 of 4) after wide local excision.

Angiosarcoma of the Breast

Angiosarcoma is a rare tumor comprising 3% to 9% of all breast
sarcomas; it accounts for about 1% of all breast primary malignancies.
[ref: 96] These tumors tend to be large, soft, and ill defined,
frequently with focal areas of hemorrhagic necrosis; they are somewhat
difficult to diagnose histologically because of the normal appearance
of some of the blood vessels. [ref: 106] In a report by Chen and
co-workers, [ref: 106] 37% of angiosarcomas were misinterpreted as
benign tumors at initial biopsy. The tumors are anaplastic and are
composed of unevenly dilated vascular channels lined by flat
endothelial cells. Some authors have correlated survival with the
degree of histologic tumor differentiation.

Simple excision of the tumor is frequently followed by local
recurrence [ref: 106]; therefore, total mastectomy or generous wide
local excision and radiation therapy are the recommended methods of
treatment. More radical procedures may be required for larger tumors,
particularly those invading adjacent structures. Lymph node metastases
are uncommon; according to Bundred and associates, [ref: 84] axillary
node sampling or dissection appears to be unnecessary because the
primary mode of tumor spread is hematogenous. Sellke and colleagues
[ref: 677] stated that, of 164 cases reported in the literature, 21
patients survived longer than 5 years and 8 survived longer than 10
years without evidence of disease.

Radiation therapy has occasionally been used in treatment of these
patients, but no specific reports are available. If a patient requires
irradiation for this lesion, we recommend doses and techniques similar
to those outlined for the treatment of breast carcinoma. Several
authors, including Donnell and associates [ref: 171] and Rosner, [ref:
622] have reported better survival with adjuvant chemotherapy. Antman
and colleagues [ref: 16] described five patients with angiosarcoma
treated with a combination of surgery, post-operative irradiation, and
adjuvant chemotherapy (doxorubicin alone or cyclophosphamide combined
with dacarbazine), some of whom survived 20 to 38 months after
therapy. Bundred and associates [ref: 84] believe that adjuvant
chemotherapy cannot be justified even in women with poorly
differentiated angiosarcoma of the breast, because the behavior of the
tumor is so unpredictable.

Adenocarcinoma in Axillary Lymphadenopathy Without Detectable Breast
Primary Cancer (Stage T0N1b)

The radiation oncologist is sometimes faced with the puzzling clinical
presentation of isolated axillary lymphadenopathy with adenocarcinoma,
with no clinical or radiologic evidence of a primary tumor in the
breast or any other anatomic site. [ref: 816] In addition to a careful
physical examination including the breast, bilateral mammograms and
chest x-ray films should be obtained. An exhaustive radiographic
workup, including CT scan of the chest, upper gastrointestinal
studies, barium enema, and intravenous pyelogram, is not warranted.
[ref: 97] Often, after careful examination of mastectomy specimens,
the primary tumor in the breast cannot be demonstrated (Table 50-19).
These patients have a relatively good prognosis, with survival rates
of 50% to 80% at 5 and 10 years. [ref: 212,550]

Whereas some authors advise mastectomy and axillary dissection, [ref:
24] an alternative is irradiation of the breast and the regional
lymphatics. Although a primary tumor often is not identified on
mammograms and boost doses cannot be delivered to the breast in
general, the breast is treated with doses of 50 Gy and the
axillary/supraclavicular lymph nodes with 50 Gy, with a boost of 10 to
15 Gy to the axillary fossa, where the initial lymph nodes were
palpated. Because of the excellent prognosis of these patients and the
infrequency of distant metastases, adjuvant chemotherapy may not be
warranted. [ref: 816]

Campana and associates [ref: 97] reported on 31 patients, some of whom
were previously included in publications by Vilcoq and colleagues.
[ref: 816] Initial treatment consisted of resection of the involved
lymph nodes followed by irradiation in 14 patients, axillary
dissection and radiation therapy in 8 patients, radiation therapy
followed by axillary dissection in 6 patients, irradiation and
modified radical mastectomy in 1 patient, and irradiation alone in 2
patients. The radiation therapy techniques included breast irradiation
in 30 patients using standard techniques; dose delivered to the
midpoint of the breast was 62 Gy. All 31 patients received radiation
therapy to the regional lymphatics (axillary, supraclavicular, and
internal mammary chains) to doses of 60 Gy or higher; 10 patients
received adjuvant chemotherapy. All 31 patients were monitored, with a
median follow-up of 9 years. By the time of the report, 8 locoregional
recurrences had been detected; all were histologically proven
infiltrating ductal carcinoma. Four of the 8 patients had isolated
breast recurrences at 63, 90, 136, and 162 months after treatment; 3
of these 4 patients were salvaged by modified radical mastectomy, and
another was given further irradiation for a recurrence in an initially
underdosed region. Three of 8 patients had breast recurrences
associated with axillary relapse, and another developed low cervical
lymph node recurrence. Two contralateral breast tumors occurred 1 and
9 years after treatment of the ipsilateral lesion. The overall 5- and
10-year survival rates were 76% and 71%, respectively. The risks of
locoregional recurrence at 5 and 10 years were 14% and 25%,
respectively, and the risks of developing distant metastases were
23.5% and 29%, respectively. Cosmetic results were evaluable in 24
patients; cosmesis was reported to be good in 19 (75%) and fair in 5
patients. Six patients had limitation of shoulder movement, 2
experienced arm edema, and 2 had asymptomatic focal pulmonary
fibrosis.

Baron and co-workers [ref: 38] described results in 35 patients with
axillary metastasis without evidence of a breast cancer, including
mammographic evaluation. Twenty-eight patients were treated with
mastectomy, and 7 were managed by limited resection, axillary
dissection and irradiation, or both. Twenty-two (67%) of 33 breast
specimens contained carcinoma (invasive in 18, in situ in 4). The
actuarial 5-year survival rate was 77% after mastectomy and 65% after
breast-preserving surgery and irradiation. Five patients had
contralateral breast cancer treated either before or after therapy for
the axillary carcinoma with occult breast tumors. The 5-year survival
rate was comparable for patients receiving or not receiving adjuvant
chemotherapy (79% and 77%, respectively).

Sixty cases of axillary histologic metastasis were analyzed by Merson
and associates. [ref: 496] The number of pathologic metastatic nodes
was one in 13 patients, two to three in 10 patients, and four or more
in 23 patients; the number of metastatic nodes was not evaluable in 14
cases. Extranodal invasion was seen in 92% of cases. Thirty-three
patients underwent breast surgery at the time of histologic diagnosis
of the axillary metastases; 6 patients were treated with radiation
therapy to the breast, and 17 patients did not receive any immediate
treatment to the breast (9 of these later developed a primary breast
carcinoma). Thirty-seven of 60 patients received adjuvant therapy (29
chemotherapy, 8 tamoxifen). The 5- and 10-year survival rates were 77%
and 58%, respectively. Survival was equivalent for patients treated
with immediate surgery plus radiation therapy and for patients who
were observed without treatment to the breast. Adjuvant treatment did
not improve prognosis.