Breast cancer: A 21 year experience with conservative surgery and radiation

Evidence is presented from a study of 680 patients followed over a period of 21 years that conservative treatment of breast cancer by local excision of the primary tumor followed by breast irradiation yields results equivalent to the traditional radical approach, with the added benefit of an excellent cosmetic result and improved quality of life. The relative survivals were 83 % at 5 years and 71 % at 10 years. There was no difference in survival when radiation was given. Breast irradiation significantly reduced relapse in the breast, but axillary irradiation did not influence relapse at this site. Relapse in the breast alone was not detrimental to survival if treated appropriately. Axillary relapse indicated a much poorer prognosis as might be expected.     

Breast conservation in the treatment of early breast cancer. A 20-year follow-up

Two hundred sixty-three patients with unilateral primary breast cancer, treated by local excision of the primary tumor and radical radiation therapy between 1954 and 1969, were followed up for a minimum of 10 years and a maximum of 20 years. The treatment plan delivered 4500 rad in fractions of orthovoltage irradiation to five fields: tangential breast fields, axilla with posterior axillary field, parasternal and supraclavicular, with a subsequent boost of 1000 rad to the primary tumor site, axilla, and supraclavicular fossa. Patients were clinically staged using the TNM (UICC) system; 115 patients had tumors less than 2 cm in diameter and a clinically negative axilla (T1N0N1a), 96 had tumors 2 to 5 cm in diameter with a clinically negative axilla (T2N0N1a), and 52 had tumors less than 5 cm in diameter and clinical axillary lymph node metastases (T1T2N1b). The actuarial relapse-free survival of patients with T1N0N1a tumors was 72% at 5 years, 59% at 10 years, and 47% at both 15 and 20 years. The relapse-free survival of patients with T2N0N1a tumors was not statistically different (P greater than 0.05). A significantly worse survival was observed in patients with clinical axillary lymph node metastases (T1T2N1b), with a survival of 37% at 5 years, 29% at 10 years, 23% at 15 years, and 22% at 20 years, when compared with patients with clinically negative lymph nodes (P less than 0.01). Locoregional relapse occurred in 22%, at 10 years, of those patients with T1 or T2N0N1a tumors and 52% of the patients with T1T2N1b tumors. The pattern of locoregional relapses indicated that approximately 50% occur at least 5 years after treatment; this contrasts with the pattern of early locoregional relapse after mastectomy. The commonest sites of relapse were in the breast in 19% and axilla in 6% of patients with T1 or T2N0N1a tumors. There was no attenuation of the radiation dose administered at the site of a subsequent relapse. Surgery for radiation failure produced a 42% crude relapse-free survival at 5 years after salvage mastectomy in those patients originally treated for T1 or T1N0N1a tumors. The results of this study suggest that a significant proportion of patients relapse locally over a prolonged period after breast conservation. The evolution of new radiation techniques may provide better locoregional control and early salvage surgery may result in improved long-term survival.     

Effect of combined transient androgen deprivation and irradiation following radical prostatectomy for prostatic cancer

Purpose: To evaluate whether transient androgen deprivation improves outcome in patients irradiated after radical prostatectomy for locally advanced disease, persistent or rising postoperative prostate specific antigen (PSA), or local recurrence.Methods and Materials: Records of 105 consecutive patients who were treated with pelvic irradiation after radical retropubic prostatectomy between August 1985 and December 1995 were reviewed. Seventy-four patients received radiation alone (mean follow up: 4.6 years), and 31 received transient androgen blockade with a gonadotropin-releasing hormone agonist (4) androgen receptor blocker (1) or both (24) beginning 2 months prior to irradiation (mean follow-up 3.0 years) for a mean duration of 6 months. Two of these patients were excluded from further analysis because they received hormonal therapy for more than 1 year. Patients received a prostatic fossa dose of 60–70 Gy at 2 Gy per fraction; 48 patients also received pelvic nodal irradiation to a median dose of 50 Gy. Survival, freedom from clinical relapse (FFCR), and freedom from biochemical relapse (FFBR) were evaluated by the Kaplan-Meier method. Biochemical relapse was defined as two consecutive PSA measurements exceeding 0.07 ng/ml.Results: At 5 years after irradiation, actuarial survival for all patients was 92%, FFCR was 77%, and FFBR was 34%. FFBR was significantly better among patients who received transient androgen blockade before and during radiotherapy than among those treated with radiation alone (56 vs. 27% at 5 years, p = 0.004). FFCR was also superior for the combined treatment group (100 vs. 70% at 5 years, p = 0.014). Potential clinical prognostic factors before irradiation did not differ significantly between treatment groups, including tumor stage, summed Gleason histologic score, lymph node status, indication for treatment, and PSA levels before surgery or subsequent treatment. Multivariate analysis revealed that transient androgen deprivation was the only significant predictor for biochemical failure.Conclusion: This retrospective study of irradiation after radical prostatectomy suggests that transient androgen blockade and irradiation may improve freedom from early biochemical and clinically evident relapse compared to radiotherapy alone, although more prolonged follow-up will be needed to assess durability of impact upon clinical recurrence and survival rates.     

Randomized clinical trial to assess the effectiveness of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer.

BACKGROUND: Although the conservation management of breast cancer has become a routine method of treatment in most centers, there is still considerable controversy surrounding the ultimate minimum treatment required for node-negative breast cancer to achieve adequate local control. PURPOSE: Our purpose was to assess the value of breast irradiation in reducing breast relapse following conservation surgery for node-negative breast cancer. We attempted to define low-risk groups of women for breast and distant site relapse (i.e., recurrence outside the breast) who might be spared breast irradiation or adjuvant systemic therapy. METHODS: Eight hundred thirty-seven patients were randomly assigned to receive radiation therapy or no radiation therapy following lumpectomy and axillary dissection for node-negative breast cancer. RESULTS: Breast irradiation reduced relapse in the breast from 25.7% in the controls to 5.5% in the irradiated patients. There was no difference in survival between the two groups (median follow-up, 43 months). A low-risk group (less than 5% chance of relapse in the breast without irradiation) could not be defined. Tumor size (greater than 2 cm), age (less than 40 years), and poor nuclear grade were important predictors for breast relapse. Age (less than 50 years) and poor nuclear grade were important predictors for mortality. The presence of ductal carcinoma in situ did not predict breast relapse. CONCLUSIONS: Breast irradiation significantly reduces breast relapse, but it does not influence survival. Important predictors of breast relapse are age, tumor size, and nuclear grade, but not the presence of ductal carcinoma in situ. Age and, in particular, nuclear grade predict survival. IMPLICATIONS: Further follow-up may define an acceptable low-risk group for breast relapse. Until then, we recommend that all patients receive breast irradiation. Systemic adjuvant therapy should be considered for patients with poor nuclear grade tumors.     

Radiotherapy for locoregional relapses of rectal carcinoma after initial radical surgery: definite but limited influence on relapse-free survival and survival.

A group of 95 patients, treated with irradiation for relapse after radical surgery as only initial treatment modality for a rectal carcinoma was studied. The term locoregional relapse relates to evidence of tumor recurrent in the pelvis or the perineal area. Seventy-six patients presented with locoregional relapse only, and 19 patients presented with locoregional relapse and concomitant distant metastases. All patients were irradiated at the site of locoregional relapse. Total dose of irradiation was resp. 44 Gy median (range 6-66 Gy) and 40 Gy median (range 6-50 Gy). In the group of patients with locoregional relapse only, recurrence-free survival and survival after radiotherapy were, respectively, 23% and 61% at 1 year, and 6% and 13% at 3 years. In the group of patients with concomitant distant metastases, survival after radiotherapy was even worse, 33% at one year, and nihil at 3 years. Recurrences after radiotherapy occurred early during follow-up with 75% of the recurrences being recorded during the first year of follow-up. Recurrent or persistent disease inside the irradiation volume was the most important clinical problem in both groups, being documented in, respectively, 43/76 and 7/19 (7/13 if six patients were excluded with a survival of less than 3 months from onset of therapy). In the group of patients with locoregional relapse only, using recurrence-free survival as the endpoint, dose of irradiation (p = 0.01) was a significant multivariate prognostic factor and using survival as the endpoint, dose of irradiation (p = 0.005) and grade of tumor differentiation (p = 0.002) were significant. Potentials of current radiotherapy regimes are limited. Therefore, maximal initial treatment is warranted. In the event of a relapse after initial radical surgery, one should opt for either more aggressive standard therapy, or either new combined modalities approaches should be studied.     

Preoperative or postoperative irradiation as adjunctive treatment with radical mastectomy in breast cancer

Results from the standpoint of survival rates and locoregional failures are compared in three series of patients having had a radical mastectomy for breast cancer: (1) radical mastectomy alone for the patients who had essentially outer quadrant lesions and a negative axilla; (2) postoperative irradiation when the axillary nodes were positive and/or the tumor was centrally located or in the inner quadrants; and (3) preoperative irradiation for patients with an outside biopsy presenting with a very disturbed breast with edema and ecchymosis, and in a small group of patients with a lesion of clinically borderline operability. The ten-year survival rates are identical in the three groups. In the radical mastectomy alone group, 14% of the patients had positive axillary nodes, in the preoperative irradiation group 30% (probably one half of the true incidence without preoperative irradiation), and in the postoperative group, 71%. This data is indicative that irradiation, either pre- or postoperatively, has survival benefits since there is direct relationship between the percentage of patients with positive axillary nodes and the survival rates. However, there is no evidence that preoperative irradiation is superior to postoperative irradiation.     

Analysis of local-regional relapses in patients with early breast cancers treated by excision and radiotherapy: experience of the Institut Gustave-Roussy

Between 1970 and 1981, 436 patients with T1 and small T2 breast carcinoma were treated by tumor excision followed by radiotherapy at the Institut Gustave-Roussy. The mean follow-up was 5 years, with 50% of patients followed 5 years. Twenty-four patients have experienced a local-regional (LR) relapse for an actuarial LR control rate of 93% at 5 years and 90% at 10 years. Potential prognostic factors for all 24 local-regional recurrences and for the subgroup with relapses in the breast were analyzed. A high Bloom grade and low Nominal Standard Dose (NSD) were significant prognostic factors for predicting LR relapse in both groups. Disease-free survival (from initial presentation) was not adversely affected by a solitary breast recurrence, when patients with successful salvage treatment were considered disease free. However, the group of patients with nodal or dermal recurrences had a much worse prognosis. This paper describes the natural history of breast cancer following a local-regional relapse in irradiated patients without mastectomy. Most importantly, we observed that breast relapses following radiotherapy become clinically apparent more slowly than chest wall failures after mastectomy, and if detected early, that these patients may be successfully retreated.     

Nasopharyngeal carcinoma in the young

This study reviewed 25 patients with nasopharyngeal carcinoma who were less than 30 years of age at diagnosis. Lymphoepithelionna was the histological diagnosis in all but 3. The anatomical extent of disease was described using the TNM system. Local bone destruction was present in 10 patients at diagnosis; cervical nodes were clinically positive in 88 % of patients of which 54 % were bilateral. All were treated with radical irradiation using a variety of techniques and doses. No patient received adjuvant chemotherapy. Overall survival was 70 % at 5 years and 57 % at 10 years from diagnosis. There were 5 relapses at the primary site, 2 in cervical nodes and 8 in bone or lung. Primary site relapse was not demonstrated to be dependant on T group or radiation dose, but likely related to inadequacy of original treatment volume. Distant metastases at first relapse correlated with advanced T and N and were the principal obstacle to successful treatment. Adjuvant chemotherapy is suggested as an important target for further study.     

Primary non-Hodgkin's lymphoma of the breast: retrospective analysis of prognosis and patterns of failure in two Australian centers

The breast is an uncommon site of presentation for primary non-Hodgkin's lymphoma, with prognosis and patterns of relapse still not clearly defined. A retrospective analysis of 21 patients presenting to 2 Australian centers during a 20-year period is presented. All patients were women and had a median age of 62 years. Fifteen patients (71%) had localized disease (12 unilateral and 3 bilateral), and 6 (29%) had regional lymph-node involvement. Histology was predominantly intermediate grade, with diffuse large B-cell lymphoma (DLBL) in 16 cases (76%). The most common treatment program was partial mastectomy followed by chemotherapy and radiation therapy (n = 12). Complete response (CR) to treatment was exhibited in 19 patients (90%), 11 of whom subsequently experienced relapse. Including the 2 patients who failed to exhibit an initial CR, the median time to disease progression was 23.4 months (range, 0-143 months), with a 5-year disease-free survival rate of 38% (+/- 12%). The actuarial median survival of all patients was 3.8 years, with bilateral breast involvement at presentation the only significant prognostic factor. The contralateral breast was the site of initial relapse in 3 patients (17%), all of whom subsequently died of disease. The actuarial rate of central nervous system (CNS) recurrence at 8 years was 39% (+/- 14%), occurring only in patients with diffuse large-cell histology. Our analysis suggests that DLBL presenting in the breast has a poor prognosis and characteristic patterns of failure. Targeted strategies such as CNS prophylaxis and contralateral breast irradiation might therefore improve prognosis and should be prospectively studied.     

Prognostic value of hormone receptors in breast cancer

The aim of this study was to establish the role of estrogen receptor (ER) and progesterone receptor (PgR) as prognostic indicators for early recurrence and survival. In all, among breast cancer patients, 166 patients who had undergone radical or extended radical mastectomy were studied. These patients were treated with adjuvant chemotherapy alone for 2-3 years after surgery. No patients had adjuvant endocrine therapy. Local recurrence and/or distant metastases were treated by endocrine therapy and/or chemotherapy. The relapse-free interval was not different between the ER-positive and ER-negative patients. The postrelapse survival curve was significantly different between the two groups. There was no significant difference in the relapse-free interval and the postrelapse survival curve between the PgR-positive and PgR-negative patients. These results suggest that ER is a good predictor of the response to endocrine therapy given after relapse, but not of early recurrence.     

The Christie hospital adjuvant tamoxifen trial--status at 10 years

From November 1976 to June 1982, a randomised clinical trial was carried out at the Christie Hospital, Manchester, to test the clinical efficacy of tamoxifen (TAM) as an adjuvant to surgery for patients with operable breast carcinoma. Following surgery, premenopausal women were randomly allocated to have either TAM 20 mg day-1 for one year or an irradiation menopause (the previous standard treatment). Postmenopausal women had TAM 20 mg day-1 for one year or no further treatment (Controls). A total of 1005 patients were entered into the trial of whom 961 are evaluable at 10 years from the inception. At 10 years the analysis shows no significant difference in overall and disease free survival between premenopausal women given TAM or an irradiation menopause. For premenopausal node negative patients there would appear to be a trend in favour of the TAM treated patients with a 93% ten year survival vs. 82% for the irradiation menopause group (P = 0.09). When the disease free survival of all 961 patients is analysed, allowing for node status, then there is a marked trend in favour of the TAM treated patients (P = 0.07). Of the patients originally allocated to TAM 47% had an irradiation menopause on relapse and 73% of the postmenopausal control patients had TAM on relapse. The incidence of side effects and second primary tumours is discussed as well as the possible effects of varying the length of time over which adjuvant TAM is administered.     

Cure of early-stage Hodgkin's disease with subtotal nodal irradiation

Ninety-four consecutive patients with Stage I or II Hodgkin's disease who presented supradiaphragmatically were treated with radiation therapy alone at the Mallinckrodt Institute of Radiology from January 1978 through December 1986. Fifty-two patients (55%) were staged pathologically, and 42 (45%) were staged clinically. The latter included lymphangiography and/or abdominal computed tomographic scan. Most patients with B symptoms and/or bulky disease were excluded from this series. Seventy-four patients were treated with subtotal nodal irradiation (mantle and periaortic fields). The spleen was treated if the patient had not undergone splenectomy. Twenty patients received mantle irradiation only. No patient received total nodal irradiation. All patients had an initial complete response. With a minimum follow-up of 7 months (median, 7.7 years; seven patients died before 3 years of follow-up, but all other patients had at least 3 years of follow-up), 81 patients (86%) remained disease-free. Six of 52 (12%) of the pathologically staged group had a relapse, as did seven of 42 (17%) of the clinically staged group (P = 0.68). Eight of 57 Stage I patients versus five of 37 Stage II patients had a relapse (P greater than 0.99). Analysis of disease-free survival by age, histologic findings, sex, and sites of involvement did not predict relapse. The pelvis was the most common site of failure (nine patients, 10%). However, only three patients (3%) failed in the pelvis alone. These results indicate that patients who, after adequate clinical staging with selective use of staging laparotomy, are found to have Stage I and II Hodgkin's disease may be treated with subtotal nodal irradiation with a high rate of cure.     

Prognostic implications of age in breast cancer patients treated with tumorectomy and irradiation or with mastectomy

Conservation breast treatment is of particular interest to young women, but whether saving the breast carries a penalty in shorter survival or local-regional recurrent disease has not been well-established. At The University of Texas M.D. Anderson Hospital and Tumor Institute at Houston, 1161 patients treated prior to 1983 with Stage I or II breast cancer were reviewed. Of these patients, 378 were treated with tumorectomy plus irradiation, and 783 were treated with radical or modified radical mastectomy. The two patient groups were compared relative to local-regional disease recurrence and overall and disease-free survivals. Local recurrences in the breast appear to be more frequent in patients less than or equal to 35 years of age treated with tumorectomy and irradiation than in patients older than 35 years, but in patients aged less than or equal to 50 or greater than 50 or less than or equal to 35 or greater than 35 years, there was no significant statistical difference between tumorectomy and irradiation or mastectomy nor was there a difference in disease-free survival. Overall survival rates favored patients treated by tumorectomy and irradiation.     

Patterns of local-regional recurrence and results in Stages I and II breast cancer treated by irradiation following limited surgery. An update

One hundred forty-six women with Stage I and Stage II breast cancer received radical radiotherapy after having excisional biopsy ( lumpectomy ) at Massachusetts General Hospital between 1956-1978. They were grouped according to age: those younger than 49 years and those older than 50 years. The 5-year survival rates were 93 and 73% for patients with Stage I and Stage II cancer, respectively; the corresponding 5-year relapse survival rates were 75 and 56%. The local recurrence rate was 8% in patients with Stage I disease and 17% in those with Stage II disease. Survival was not significantly affected by patients' age, by the presence or absence of blood vessel or lymphatic involvement, or by the addition of adjuvant chemotherapy. No major complications occurred. Modification in radiation dose and technique resulted in improved overall survival and local control. Limited surgery followed by radical radiation therapy offers a therapeutically effective, cosmetically acceptable alternative to radical surgery for early stage breast cancer.     

Long-term follow-up of patients with Stage III follicular lymphoma treated with primary radiotherapy at Stanford University

PURPOSE: To report the long-term survival and late toxicity data of Stage III follicular lymphoma patients treated with primary radiotherapy.METHODS AND MATERIALS: Sixty-six patients with Stage III follicular small cleaved (FSC) or follicular mixed (FM) non-Hodgkin's lymphoma were treated with total lymphoid irradiation (61 patients) or whole body irradiation (5 patients) as their primary treatment modality from 1963 to 1982 at Stanford University. Adjuvant chemotherapy was given to 13 patients. RESULTS: Median follow-up was 9.5 years with a range of 0.5-24.3 years. Median overall survival, cause-specific survival, freedom from relapse, and event-free survival were 9.5, 18.9, 7.1, and 5.1 years, respectively. Few initial relapses or lymphoma-related deaths were seen beyond the first decade of follow-up. Patient age and number of disease sites were the two strongest predictors of overall survival. The cohort of patients with limited Stage III disease demonstrated an 88% freedom from relapse and a 100% cause-specific survival with up to 23.5 years follow-up. CONCLUSION: The long-term survival data for Stage III FSC or FM non-Hodgkin's lymphoma treated with primary radiotherapy are at least comparable and possibly better than results achieved with other therapeutic approaches. Patients with limited Stage III disease do particularly well. Whether these results are superior to an initial approach of deferred therapy until clinically indicated is currently unknown.     

The place of brachytherapy in the treatment of carcinoma of the tonsil with lingual extension

One hundred forty-four of 170 patients (85%) were seen with cancer of the tonsil and received radical irradiation between 1959 and 1980. A 39% crude 3-year disease-free survival rate and a 51% locoregional control rate were observed. Locoregional relapse related to T Stage was 6, 43, 58, and 64% for T1, T2, T3, and T4, respectively. Fifty-four of 144 patients (37%) showed tongue extension, 20% in T1-T2 stages and 50% in T3-T4 stages. Local relapse was 64% and the 3-year disease-free survival rate was 23% in 39 patients with tongue extension treated with external irradiation alone, versus 33 and 43% respectively for 90 patients with no tongue extension. The increase of lymph node metastases or neck recurrences was not related to tongue extension. In 15 patients with tongue extension, treated with external radiation plus brachytherapy, the local relapse was 40% and the 3-year survival rate 60%. External irradiation plus brachytherapy was significantly related to lower local relapse and increased survival rate compared to external irradiation alone in cancer of the tonsil with tongue extension. The combined modality was not associated with increased risk of radiation complications.     

Changing pattern of the detection of locoregional relapse in breast cancer: the Edinburgh experience

The guidelines for follow-up of breast cancer patients concentrate on the first 3-5 years, with either reduced frequency of visits or discharge after this. They also recommend mammography, but no evidence exists to inform frequency. We analyse treatable relapses in our unit from 1312 patients with early stage breast cancer treated by breast conserving surgery (BCS) and postoperative radiotherapy between 1991 and 1998 to assess appropriateness of the guidelines. A total of 110 treatable relapses were analysed. Treatable relapse developed at 1-1.5% per year throughout follow-up. Forty-eight relapses were in ipsilateral breast, 25 ipsilateral axilla, 35 contralateral breast, 2 both breasts simultaneously. Thirty-seven relapses (33.5%) were symptomatic, 56 (51%) mammographically detected, 15 (13.5%) clinically detected, 2 (2%) diagnosed incidentally. Mammography detected 5.37 relapses per 1000 mammograms. Patients with symptomatic or mammographically detected ipsilateral breast relapse had significantly longer survival from original diagnosis (P=0.0002) and from recurrence (P=0.0014) compared with clinically detected. Treatable relapse occurs at a constant rate for at least 10 years. Clinical examination detects a minority (13.5%). Relapse diagnosed clinically is associated with poorer outcome. Long-term follow-up based on regular mammography is warranted for all patients treated by BCS.     

Colloid cancers of the breast. Value of radiotherapy. A series of 138 cases treated at the Curie Institute

A series of 138 mucinous breast carcinomas was treated at the Institut Curie from 1970 to 1980: 107 were diagnosed as "pure" mucinous carcinoma and 31 as "mixed" mucinous carcinomas. Fifty per cent of the cases were stage T2 and 78% N0-N1a. Treatment methods were radical mastectomy in 113 cases (82%) with pre-operative irradiation for 37 patients and post-operative irradiation for 14 patients. A conservative treatment was used for 25 patients, consisting either of lumpectomy followed by radiotherapy (in 15 cases) or radiotherapy alone (in 10 cases). The five-year actuarial survival rate was 81% for the "pure" group and 87% for the "mixed" group; it was 70 and 75%, respectively, at ten years follow-up. In this series, survival was not influenced by the type of treatment. The efficacy of radiotherapy was evaluated from the local recurrence rate: only four local failures among the 25 conservative treatments were noted. Our conclusion is that radiotherapy, with or without lumpectomy, is efficient in mucinous breast carcinoma and could be useful in selected cases.     

Long-range results for breast cancer patients treated by radical mastectomy and postoperative radiation without adjuvant chemotherapy: an update

Between 1963 and 1977, 941 patients with carcinoma of the breast received, at the University of Texas M.D. Anderson Cancer Center, peripheral lymphatic irradiation alone or with chest wall irradiation after a radical or modified radical mastectomy. None of the patients received adjuvant chemotherapy. The incidence of patients with histologically involved axillary nodes was 70%. The lymphatics of the apex of the axilla, of the supraclavicular area, and of the internal mammary chain were irradiated in patients with histologically positive axillary nodes and/or in patients with central or inner quadrant primaries regardless of the axillary status. When in 1963 an electron beam became available, chest wall irradiation has been added to the peripheral lymphatics irradiation, primarily when there was a heavy infestation of the axillary nodes. The disease-free survival curves tend to flatten out at 10 years. At 10 and 20 years, the disease-free survival rates are respectively 55% and 50% for all patients, 44% and 40% for all patients with positive nodes, 56% and 48% for the patients with one to three positive nodes, and 33% and 30% for the patients with four or more positive nodes. The comparison of the mortality curves between the general population and the breast cancer patients seems to indicate a cured fraction, since the curves become parallel at 17 years. The highest incidence of failures is between 0 and 5 years, still a significant incidence between 5 and 10 years, but after 10 years the incidence of failures is relatively small.     

Prognostic Value of Tumor Infiltrating Lymphocytes in Locally Advanced HER2 Enriched Breast Cancer

Purpose: We aim to study the association between stromal tumor infiltrating lymphocytes (TILs) level and disease free survival (DFS) in a group of ER and PR negative, HER2+ locally advanced breast cancer patients who underwent curative intent surgery. Methods: This is a retrospective cohort study including 66 locally advanced hormone receptor-negative; HER2+ breast cancer patients presented between 2013 and 2015 at NCI-Cairo, Egypt. Enrolled patients had at least clinically T3 and/or node positive disease either clinically or radiologically. Metastatic workup included CT and bone scans or PET-CT. Patients with hormone receptor positive, HER2 negative, inadequate paraffin block and who lost follow up before or immediately after curative surgery were excluded. Patients were followed from breast surgery till relapse date for a minimum of 36 months. TILs and CD8 antigen were assessed on paraffin-embedded blocks using immunohistochemistry. Results: Patients with a median age of 52 years presented with clinical T3 stage (53%) and N1 stage (61%). Modified radical mastectomy was performed in 79%. Only 41% received neoadjuvant chemotherapy and 56% received trastuzumab. TILs were 50, 17 and 33% for absent, intermediate and extensive groups and CD8+ lymphocytes were present in 80% of cases. At the end of follow-up period, 23 patients (35%) were found to have disease recurrence either loco-regional (22%) or distant (78%). TILs were 14, 4 and 5% for absent, intermediate and extensive respectively; while CD8+ lymphocytes were absent in 6% and present (≥1%) in 17%. Higher DFS was recorded for patients with extensive TILs level only who received trastuzumab. Conclusion: High TILs is good prognosis in HER2 enriched breast cancer provided that patients received HER2 directed therapy. Moreover, CD8+ lymphocytes are highly representative and maybe used as an alternative for TILs. We recommend considering TILs and specifically CD8+ as one of the risk factors that predict prognosis of HER2+ breast cancer.