Surgical treatment of minimal breast carcinoma]

The surgical approach to minimal breast cancer is still under discussion. In fact by the term "minimal" three lesions are meant, namely "lobular carcinoma in situ", "intraductal carcinoma" and invasive "microcarcinoma". It is really difficult to indicate appropriate treatment for these tumors, also because the series reported in the literature are few and represented by a small number of cases. The present paper is a critical review of the literature on the subject. According to the most recent view lobular carcinoma in situ and intraductal carcinoma demand for radical surgery (total mastectomy) due to the high percentage of multicentricity and bilaterality of these lesions. More particularly with regard to lobular carcinoma in situ recent reports claim for a "wait and see" policy which is gaining favour, on the ground that the risk of developing invasive cancer in women with lobular carcinoma in situ is not so high and that the period of time between diagnosis of the lobular carcinoma and the development of the invasive cancer is usually very long. On the other side, for intraductal carcinoma, axillary dissection seems to be pleonastic due to the low percentage of secondary deposits in axillary lymph-nodes (1-3%) in women operated on for intraductal carcinoma. Invasive microcardinomas, less than 5 mm in diameter, should be considered as T1N0 tumors; actually there is no reason to treat them by a more conservative surgery than is done for T1N0 cancers, as they present the same involvement of the axillary lymph nodes. In a small series of 38 microcarcinoma observed at the Milan Cancer Institut N+ cases were 27%.     

Mammographically detected duct carcinoma in situ. Frequency of local recurrence following tylectomy and prognostic effect of nuclear grade on local recurrence

Seventy-nine patients with mammographically detected foci of duct carcinoma in situ (DCIS) of histologically confirmed extents of 25 mm or less, were treated by tylectomy without irradiation or axillary dissection. Adequacy of excision was confirmed histologically, by radiographic-pathologic correlation and by postoperative mammographic examination. Eight patients (10.1%) have recurred locally in the immediate vicinity of the biopsy site. Four patients developed recurrent in situ disease identified mammographically, and all were initially treated by reexcision. One of these patients subsequently elected to undergo mastectomy; no residual in situ or invasive disease was detected in the breast or in axillary lymph nodes. Four patients developed recurrent invasive disease; 50% of these recurrences were detected mammographically. All patients were treated by mastectomy with node dissection. Three had confirmed minimal invasive carcinomas and were N0, one patient had a 13-mm invasive lobular carcinoma with a single Group I micrometastasis. All patients, including those treated for a recurrence, are presently free of disease but three patients died of heart disease. Nuclear grade would appear to identify subsets of DCIS more likely to produce local failure after tylectomy alone. Duct carcinoma in situ with high-grade nuclear morphology and comedo-type necrosis was associated with a 19% local recurrence rate after an average interval of 26 months; only one of ten patients with intermediate-grade DCIS developed a local recurrence at 87 months; and none of 33 patients with DCIS of micropapillary/nonnecrotic cribriform type and low-grade nuclear morphology developed local recurrence in the follow-up period.     

Survival in bilateral breast cancer

The presence of bilateral invasive breast cancer places the patient in a state of double jeopardy. At Memorial Sloan-Kettering Cancer Center, the overall 10-year recurrence rate for unilateral Stage I breast cancer was 16%, whereas the recurrence rate for simultaneous, bilateral Stage I breast carcinoma was 29%: almost twice as high. The average 10-year survival of all patients with negative axillary nodes was 57%. In this retrospective analysis of 403 patients with bilateral primary operable breast cancer treated at Memorial Sloan-Kettering Cancer Center, significant differences were noted in the disease-free survival between patients with bilateral noninvasive cancer, bilateral invasive cancer, and the combination of invasive and in situ cancers. Bilateral intraductal cancer and lobular carcinoma in situ offered an excellent prognosis. The combination of preinvasive cancer on one side and infiltrating carcinoma on the other had the next best survival. The in situ lesion, when treated by mastectomy, did not alter the patients' life expectancy from that of the general population with unilateral breast cancer, thus indicating that surgeons should strive to detect breast cancer in its preinvasive form. The 5- and 10-year relapse-free survival of patients with bilateral invasive disease, regardless of axillary nodal status and tumor size, was 60% and 51%, respectively, for patients with a bilateral presentation and 54% and 38%, respectively, for carcinomas presenting metachronously. More important in determining prognosis, however, was the number of axillary nodes involved and the level of involvement. Invasion of bilateral axillary nodes at all levels predicted a poor prognosis. Because of this shortened survival, systemic adjuvant therapy should be considered for patients with bilateral invasive disease. The most common preinvasive breast cancer was lobular carcinoma in situ and the most frequently invasive tumor was infiltrating duct cancer. Since a contralateral breast cancer at the time of definitive treatment of the first side does not always present as a mass or with positive mammography, a random biopsy of the second breast is recommended. This should be done in the upper, outer quadrant and should include the subareolar area. With prompt adequate treatment, it is expected that survival from bilateral breast cancer should improve.     

Selective use of sentinel lymph node surgery during prophylactic mastectomy

BACKGROUND: Patients with invasive cancer identified at the time of prophylactic mastectomy (PM) will require axillary lymph node dissection for staging; therefore, many surgeons advocate sentinel lymph node (SLN) surgery at the time of PM. The current study investigates the invasive cancer rate in PM and evaluates factors associated with invasive cancer to guide SLN surgery use. METHODS: Patients undergoing PM at the M. D. Anderson Cancer Center between January 2000 and July 2005 were identified from a prospective database. Clinical, radiographic, and pathologic data were collected. RESULTS: A total of 409 patients (436 PM cases) were identified; 382 underwent contralateral PM (CPM) and 27 underwent bilateral PM (BPM). Cancer was identified in 22 of 436 PM cases (5%). Of these, 14 patients (64%) had ductal carcinoma in situ (DCIS). Only 8 patients (1.8%) had invasive cancer, with a mean tumor size of 5 mm (range, 2-9 mm). There was no difference in the occult cancer rate between CPM and BPM. No cases of invasive cancer were identified in the 23 patients with BRCA mutations. Significantly increased risk of invasive cancer in the PM breast was seen in postmenopausal patients (3.7%; P = .007), patients age >60 years (7.5%; P = .008), and patients with history of invasive lobular carcinoma (9.7%; P = .0002) or lobular carcinoma in situ (LCIS) (7.7%; P = .008). CONCLUSIONS: The frequency of cancer in PM is very low and the majority represents DCIS. Therefore, routine use of SLN surgery in all patients undergoing PM is not warranted. However, patients at higher risk for whom SLN surgery should be considered include older women and patients with a history of lobular cancer or LCIS.     

Staging and treatment of clinically occult breast cancer

Five hundred fifty-seven biopsies were performed for clinically occult mammary lesions, detected by mammography as clustered calcifications or nonpalpable masses within the breast. One hundred seventy-five cancers were demonstrated within this group, including 106 invasive carcinomas, 10 microinvasive carcinomas, 45 in situ ductal carcinomas, and 14 lobular carcinomas in situ (lobular neoplasia). No patient with in situ or microinvasive carcinoma had evidence of axillary node metastases in 33 specimens studied. However, a disturbingly high proportion of those patients with invasive carcinomas, approximately 35%, had histologically confirmed axillary node metastases, despite the small size of the primary tumors. These observations suggest that the use of the term "minimal" cancer is misleading when applied to invasive carcinoma. Staging systems for breast cancer have been imprecise when referring to nonpalpable lesions. Cancers detected as clustered calcifications only or as areas of parenchymal distortion without an accompanying mass are properly considered as T-0 cancers, with a suggested T-0(m) to indicate that the lesion was detected by mammography. However, when the mammogram indicates the presence of a mass that proves to be malignant, although the clinical examination may have been negative, the cancer should be staged according to the size of the mass on the mammogram, with the notation that it was detected by mammography, e.g., T-1(m), T-2(m), etc. The incidence of axillary node metastases even in these so-called occult cancers is significant, so that recommendations for treatment for any invasive cancer, regardless of its size, must take these observations into account. Similarly, the incidence of multifocal sites of cancer within the breast, even in the noninvasive cancers encountered, must be remembered when treatment is suggested.     

Sentinel lymph node biopsy and management of the axilla in ductal carcinoma in situ

Ductal carcinoma in situ (DCIS) of the breast historically has been a disease detected by physical examination, diagnosed by open surgical biopsy, and treated by mastectomy and axillary dissection. It is now increasingly detected by screening mammography, diagnosed by needle core biopsy, and treated by lumpectomy, with axillary dissection having been abandoned and sentinel node biopsy being used in axillary staging. However, outcomes related to sentinel node biopsy in DCIS have not been validated in well-controlled clinical trials. Current guideline recommendations are to use sentinel node biopsy when needle core biopsy is highly suspicious for invasive cancer or where there is a high-risk DCIS when lumpectomy identifies invasive breast cancer with the DCIS, or when mastectomy is performed for extensive DCIS. Routine use of sentinel node biopsy for DCIS is not supported.     

Similar long-term results of breast-conservation treatment for Stage I and II invasive lobular carcinoma compared with invasive ductal carcinoma of the breast: The University of Pennsylvania experience

BACKGROUND: The objective of the current study was to determine the long-term results of breast-conservation treatment in women with early-stage, invasive lobular carcinoma of the breast. METHODS: Between 1977 and 1995, 1093 women with Stage I and II invasive ductal carcinoma of the breast and 55 women with invasive lobular carcinoma of the breast underwent lumpectomy, axillary lymph node dissection, and radiation treatment. Overall, 49% of the women received adjuvant systemic therapy (chemotherapy and/or hormones). RESULTS: The median age was 52 years for patients in the invasive ductal group and 54 years for patients in the invasive lobular group. The median follow-up was 8.7 years and 10.2 years for patients in the invasive ductal and invasive lobular groups, respectively. A comparison of patients who had invasive lobular carcinoma with patients who had invasive ductal carcinoma showed no difference in the 10-year actuarial rates of overall survival (85% vs. 79%, respectively; P = 0.73), cause-specific survival (93% vs. 84%, respectively; P = 0.85), or freedom from distant metastases (81% vs. 80%, respectively; P = 0.76). The 10-year rates of local failure were 18% for patients with invasive lobular carcinoma and 12% for patients with invasive ductal carcinoma (P = 0.24), and the 10-year rates of contralateral breast carcinoma development for the 2 groups were 12% and 8%, respectively (P = 0.40). CONCLUSIONS: Breast-conservation treatment yielded similar long-term results for women with early-stage, invasive lobular carcinoma and women with the more prevalent invasive ductal carcinoma.     

Recommendations for women with lobular carcinoma in situ (LCIS)

Atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS) represent a spectrum of breast disease referred to as "lobular neoplasia" (LN). Although LN occurs relatively infrequently, it is associated with an increased risk of breast cancer, ranging from a three- to four-fold increased risk with ALH up to an eight- to ten-fold increased risk with LCIS. Initially regarded as a direct precursor to invasive lobular carcinoma, LCIS used to be treated by mastectomy. Subsequent studies demonstrating that the risk of invasive disease was conferred bilaterally and that subsequent cancers were of both the ductal and lobular phenotype led to the acceptance of LCIS as a marker of increased risk rather than a true precursor. Today, a diagnosis of LCIS remains one of the greatest identifiable risk factors for the subsequent development of breast cancer. As such, patients are offered one of three options: (1) lifelong surveillance with the goal of detecting subsequent malignancy at an early stage; (2) chemoprevention; or (3) bilateral prophylactic mastectomy. Paralleling changes in the management of invasive breast cancer, trends in the management of LCIS have moved toward more conservative management. However, we have made little progress in understanding the biology of LCIS and therefore remain unable to truly optimize recommendations for individual patients.     

Is axillary lymph node dissection necessary in elderly patients with breast carcinoma who have a clinically uninvolved axilla?

BACKGROUND: Axillary dissection in elderly patients with early-stage breast carcinoma who do not have palpable axillary lymph nodes is controversial because of the associated morbidity of the surgery, reduced life expectancy of the patients, and efficacy of hormone therapy in preventing recurrences and axillary events. METHODS: The authors performed a retrospective analysis of 671 consecutive patients with breast carcinoma who were age >or= 70 years and who underwent conservative breast surgery with axillary dissection (172 patients) or without axillary dissection (499 patients). Tamoxifen always was given. The effects of axillary dissection compared with no axillary dissection on breast carcinoma mortality and distant metastasis were analyzed using multiple proportional-hazards regression models. Because the assignment to axillary treatment was nonrandom, covariate adjustments were made for baseline variables that influenced the decision to perform axillary dissection and for prognostic factors. RESULTS: The crude cumulative incidence curves for breast carcinoma mortality and distant metastasis did not appear to differ significantly between the two groups (P = 0.530 and P = 0.840, respectively). The crude cumulative incidences of axillary lymph node occurrence at 5 years and 10 years were 4.4% and 5.9%, respectively (3.1% and 4.1%, respectively, for patients with pT1 tumors). CONCLUSIONS: Elderly patients with breast carcinoma who have no evidence of axillary lymph node involvement may be treated effectively with conservative surgery and tamoxifen. Immediate axillary dissection is not necessary but should be performed in the small percentage of patients who later develop overt axillary lymph node involvement.     

On the occurrence of focal, occult in situ and invasive carcinoma in 250 mastectomy specimens

In 1982, a total of 250 breasts were removed for cancer in the surgical departments of the Oslo City Health Department, comprising 81% of all new breast cancers reported in Oslo in 1982. Invasive ductal carcinoma (68%) and invasive lobular carcinoma (12.4%) were the predominant types. Special attention was given to the presence of occult in situ or invasive carcinomas more than 1 cm from the periphery of the main carcinoma. In 24.8% of the specimens, carcinoma in situ was found in such locations, and an additional 6.9% showed a second, occult invasive carcinoma. Carcinoma in situ was equally common in invasive ductal and invasive lobular carcinoma. Occult invasive carcinoma was predominantly found in specimens with invasive lobular carcinoma. There was a significantly increased number of lymph node metastases in patients with carcinoma in situ or second, occult primary carcinoma more than 1 cm from the periphery of the main carcinoma.     

Ultrasonographically-guided fine-needle aspiration of axillary lymph nodes: role in breast cancer management

The knowledge of the status of axillary lymph nodes (LN) of patients with breast cancer is a fundamental prerequisite in the therapeutic decision. In the present work, we evaluated the impact of fine-needle aspiration cytology (FNAC) of ultrasonographically (US) selected axillary LN in the diagnosis of LN metastases and subsequently in the treatment of patients with breast cancer. Axillary US was performed in 298 patients with diagnosed breast cancer (267 invasive carcinomas and 31 ductal carcinoma in situ DCIS), and in 95 patients it was followed by FNAC of US suspicious LN. Smears were examined by routine cytological staining. Cases of uncertain diagnosis were stained in immunocytochemistry (ICC) with a combination of anticytokeratin and anti-HMFG2 antibodies. Eighty-five FNAC were informative (49 LN were positive for metastases, 36 were negative). In 49 of 267 patients with invasive breast carcinoma (18%), a preoperative diagnosis of metastatic LN in the axilla could be confirmed. These patients could proceed directly to axillary dissection. In addition, US-guided FNAC presurgically scored 49 out of 88 (55%) metastatic LN. Of all others, with nonsuspicious LN on US (203 cases including 31 DCIS), in which no FNAC examination was performed, 28 invasive carcinomas (16%) turned out to be LN positive on histological examination. Based on these data, US examination should be performed in all patients with breast cancer adding ICC-supported FNAC only on US-suspect LN. This presurgical protocol is reliable for screening patients with LN metastases that should proceed directly to axillary dissection or adjuvant chemotherapy, thus avoiding sentinel lymph node biopsy.     

Carcinome lobulaire à cellules pléomorphes du sein. Difficultés diagnostiques: à propos d’un cas avec revue de la littérature

We report a case of a 27-years-old woman with a lesion at the right breast, incidentally noted. The patient underwent tumour resection followed by a right mastectomy type “Patey”. Microscopic analysis of the tumour had recognised an invasive pleomorphic lobular carcinoma. Invasive pleomorphic lobular carcinoma (PLC) is a distinctive aggressive subtype of invasive lobular carcinomas (ILC). It has the typical infiltrating pattern of classical ILC of diffuse single cell spread but the nuclei aremore pleomorphic. Histological differential diagnosis with ductal carcinoma may be difficult, but it is important for this difference to be done. E-cadherine is a trans-membrane glycoprotein, typically expressed in ductal carcinoma, and loss of E-cadherine expression characterises invasive and in situ lobular carcinoma.     

The role of axillary lymph node dissection in breast cancer management

Although it is generally accepted that axillary dissection provides no survival advantage in patients with breast cancer, it is commonly regarded as a reliable method of assessing nodal status and treating regional disease. However, it is time to consider eliminating routine axillary dissection in patients who are clinically node-negative. A sentinel lymph node biopsy may assess axillary nodal status while obviating a full axillary dissection. At present, axillary dissection remains the standard approach for the surgical management of all patients with invasive carcinoma of the breast, regardless of tumor size or patient age, though it is unnecessary for patients with small intraductal carcinomas.     

Isolated retromammary lymph node metastasis of breast cancer without axillary lymph node involvement: a case report with a false-negative sentinel lymph node biopsy

A 54-year-old woman visited our hospital with a palpable tumor in her left breast, which was diagnosed as invasive ductal carcinoma. Breast-conserving surgery was performed, in association with a sentinel lymph node (SLN) biopsy and back-up dissection of the axillary lymph nodes. One dyed axillary lymph node with high radioactivity was defined as an SLN, and intraoperative frozen-section analysis of the SLN was negative for metastasis. The final pathological diagnosis of the tumor was invasive ductal carcinoma, and one small lymph node, located in the retromammary space, just under the tumor, was positive for metastasis. The backup axillary lymph nodes were not metastatic. This patient was diagnosed false-negative by SLN biopsy, despite being positive for retroMLN metastasis. It should be recognized that retroMLNs are difficult to detect preoperatively, or intra-operatively, using dye or radiocolloid, if they are located in the post-tumoral retro-mammary space. RetroMLNs may be a pitfall in SLN biopsies.     

Clinicopathological features of gastric metastasis from breast cancer in three cases

The common sites for metastases from breast cancer are lymph nodes, bone, lung, liver, and brain. Gastrointestinal (GI) metastasis is rarely found or diagnosed in patients with breast cancer. This report presents three cases of gastric metastasis from breast cancer. Case 1 was a 42-year-old female diagnosed with gastric metastasis after mastectomy with axillary lymph node dissection for invasive lobular carcinoma of the left breast. Case 2 was a 54-year-old female who was diagnosed to have invasive lobular carcinoma of the left breast with systemic bone and gastric metastasis. Case 3 was a 54-year-old female who was diagnosed to have bilateral invasive ductal carcinoma of the breast with simultaneous bone and gastric metastasis. The immunohistochemical statuses for estrogen receptor, progesterone receptor, mammaglobin, and gross cystic disease fluid protein-15 (GCDFP-15) between the primary and gastric metastatic lesions were all well matched. All three cases were treated with systemic chemotherapy, hormone therapy or both, without surgical intervention for gastric lesions. Two patients with disseminated disease died 27 and 58 months after diagnosis of gastric metastasis, while one patient without organ metastasis is still alive at 56 months after diagnosis. It is important to make a correct diagnosis by distinguishing gastric metastasis from breast cancer in order to select the optimal initial treatment for systemic disease of breast cancer.     

Positron emission tomography and sentinel lymph node dissection in breast cancer

Sentinel lymph node dissection (SLND) is emerging as the preferred method of axillary staging for breast cancer patients. To further the use of noninvasive techniques in breast cancer, positron emission tomography (PET) scans have been considered as an alternative axillary staging modality. In order to compare the 2 modalities, we studied 15 invasive breast cancer patients who had undergone a preoperative PET scan before sentinel lymphadenectomy. PET scans were compared to axillary pathology results, which were defined as the greatest diameter of nodal metastases. Primary tumor sizes ranged from 0.5 cm to 5.0 cm (median,1.5 cm) and all were ductal in origin except for 1 invasive lobular and 1 mucinous carcinoma. Ten women had completion axillary dissections. Sentinel lymph node dissection was successful in all patients with completion dissections and no false-negative results. Five patients had sentinel node metastases, but PET scans identified only 1 of these patients, resulting in 4 false-negative PET scans. Missed metastases ranged in size from a micrometastatic focus identified only by immunohistochemistry to a nodal tumor measuring 11 mm in diameter. In addition, 1 woman with a PET-positive axilla was tumor free by SLND and remains free of axillary recurrence 29 months postoperatively. Two women had mediastinal uptake by PET scanning and were found to be tumor free after computerized tomography. The results of this preliminary study suggest that PET scanning using current techniques can be used as an adjunct to SLND rather than as an alternative staging technique.     

Lobular carcinoma in situ increases the risk of local recurrence in selected patients with stages I and II breast carcinoma treated with conservative surgery and radiation

BACKGROUND: Lobular carcinoma in situ (LCIS) is a known risk factor for the development of invasive breast carcinoma. However, little is known regarding the impact of LCIS in association with an invasive carcinoma on the risk of an ipsilateral breast tumor recurrence (IBTR) in patients who are treated with conservative surgery (CS) and radiation therapy (RT). The purpose of this study was to examine the influence of LCIS on the local recurrence rate in patients with early stage breast carcinoma after breast-conserving therapy. METHODS: Between 1979 and 1995, 1274 patients with Stage I or Stage II invasive breast carcinoma were treated with CS and RT. The median follow-up time was 6.3 years. RESULTS: LCIS was present in 65 of 1274 patients (5%) in the study population. LCIS was more likely to be associated with an invasive lobular carcinoma (30 of 59 patients; 51%) than with invasive ductal carcinoma (26 of 1125 patients; 2%). Ipsilateral breast tumor recurrence (IBTR) occurred in 57 of 1209 patients (5%) without LCIS compared with 10 of 65 patients (15%) with LCIS (P = 0.001). The 10-year cumulative incidence rate of IBTR was 6% in women without LCIS compared with 29% in women with LCIS (P = 0.0003). In both groups, the majority of recurrences were invasive. The 10-year cumulative incidence rate of IBTR in patients who received tamoxifen was 8% when LCIS was present compared with 6% when LCIS was absent (P = 0.46). Subsets of patients in which the presence of LCIS was associated with an increased risk of breast recurrence included tumor size < 2 cm (T1), age < 50 years, invasive ductal carcinoma, negative lymph node status, and the absence of any adjuvant systemic treatment (chemotherapy or hormonal therapy) (P < 0.001). LCIS margin status, invasive lobular carcinoma histology, T2 tumor size, and positive axillary lymph nodes were not associated with an increased risk of breast recurrence in these women. CONCLUSIONS: The authors conclude that the presence of LCIS significantly increases the risk of an ipsilateral breast tumor recurrence in certain subsets of patients who are treated with breast-conserving therapy. The risk of local recurrence appears to be modified by the use of tamoxifen. Further studies are needed to address this issue.     

In situ breast cancer

Opinion statement The clinical expression of in situ cancer varies widely but is usually occult. Diagnosis can be made by a variety of minimally invasive techniques. Treatment of lobular carcinoma in situ (LCIS) is patient-directed but generally requires only close followup. Mastectomy is the gold standard for ductal carcinoma in situ (DCIS) and is associated with low recurrence rates. Breast conservation therapy (BCT) has become an acceptable alternative. This choice of definitive therapy for DCIS depends largely on the ability to obtain negative margins. Any attempt at BCT should be coupled with the caveat of close postoperative long-term follow-up. Patients diagnosed with LCIS or who have a history of DCIS should be given the options for the use of tamoxifen for the reduction of subsequent development of invasive breast cancer. Risk versus benefits should be clearly defined.     

Apocrine differentiation in invasive pleomorphic lobular carcinoma with in situ ductal and lobular apocrine carcinoma: Case report

Invasive pleomorphic lobular carcinoma (PLC) is a distinctive aggressive subtype of invasive lobular carcinomas (ILC). We report one case of PLC with in situ PLC and ductal carcinoma in situ with apocrine features.     

The evaluation of high risk and pre-invasive breast lesions and the decision process for follow up and surgical intervention

Atypical epithelial hyperplasia, lobular carcinoma in situ (lobular neoplasia), radial scar, and ductal carcinoma in situ are considered high-risk lesions that predispose toward the future development of non-invasive or invasive breast cancer. Generally, those women with atypical epithelial hyperplasia, radial scar, or lobular carcinoma in situ can be managed conservatively by close surveillance. The minority of women may consider prophylactic mastectomy. Ductal carcinoma in situ can usually be managed by lumpectomy with or without radiation, with some patients requiring mastectomy due to extensive disease.